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山﨑哲男

徳島大学

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2024年11月14日更新

職名: 教授
電話: 088-633-7886
電子メール: tyamazak@tokushima-u.ac.jp
学歴: 1991/3: 千葉大学医学部医学科卒業
1997/3: 千葉大学大学院医学研究院博士課程修了
学位: 博士(医学) (千葉大学) (1997年3月)
職歴・経歴: 1991/4: 千葉大学附属病院研修医
1992/4: 東邦大学附属佐倉病院研修医
1997/4: 米国国立保健衛生研究所客員研究員
1998/1: 日本学術振興会海外特別研究員
2000/1: 関西医科大学肝臓研究所，助手
2003/12: 東北大学大学院医学研究科，独立フェロー・客員助教授
2007/4: 京都大学大学院薬学研究科，准教授
2009/12: 徳島大学大学院ヘルスバイオサイエンス研究部，教授

専門分野・研究分野: 生化学 (Biochemistry)

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2024年11月14日更新

専門分野・研究分野: 生化学 (Biochemistry)
担当経験のある授業科目: 免疫と疾病 (学部)
医療における人間学 (学部)
医療薬学実践演習 (大学院)
医薬品安全性学特論 (大学院)
専攻公開ゼミナール (大学院)
微生物学 (学部)
演習 (学部)
演習1 (学部)
演習3 (学部)
生物化学実習 (学部)
育薬共通演習 (大学院)
臨床病態学特論 (大学院)
薬学演習 (大学院)
薬学課題研究 (大学院)
薬科学演習1 (大学院)
薬科学特別研究 (大学院)
指導経験: 2人 (学士), 2人 (修士)

研究者総覧で最新データを確認する

2024年11月14日更新

専門分野・研究分野: 生化学 (Biochemistry)

研究テーマ: 遺伝性神経変性疾患

著書

斎藤充, 高田潤一, 髙田信二郎, 竹内靖博, 茶木修, 中村幸男, 荻野浩, 三浦雅一, 元木由美, 森脇好乃美, 森脇笙, 山﨑哲男, 吉村典子 :
骨代謝マーカーハンドブック,
メディカルレビュー社, 東京, 2022年10月. 竹島浩, 山﨑哲男, 池田篤史, 輿水崇鏡 :
医歯薬系学生のためのillustrated基礎生命科学,
京都廣川書店, 2008年.

論文

Yuki Shiro, Syouichi Katayama, Haruka Tsukamoto and Tetsuo Yamazaki :
Pro-cathepsin D prevents aberrant protein aggregation dependent on endoplasmic reticulum protein CLN6.,
Molecular Genetics and Metabolism, Vol.143, No.1-2, 108539, 2024.

(要約): We previously expressed a chimeric protein in which the small heat-shock protein αB-crystallin (αBC) is fused at its N-terminus to the C-terminus of the first transmembrane segment of the endoplasmic reticulum (ER) protein mitsugumin 23 and confirmed its localization to the ER. Moreover, overexpression of this N-terminally modified αBC was shown to prevent the aggregation of the coexpressed R120G αBC variant, which is highly aggregation-prone and associated with the hereditary myopathy αB-crystallinopathy. To uncover a molecular mechanism by which the ER-anchored αBC negatively regulates the protein aggregation, we isolated proteins that bind to the ER-anchored αBC and identified the lysosomal protease cathepsin D (CTSD) as one such interacting protein. Proteolytically active CTSD is produced by multi-step processing of pro-cathepsin D (proCTSD), which is initially synthesized in the ER and delivered to lysosomes. When overexpressed, CTSD itself prevented the coexpressed R120G αBC variant from aggregating. This anti-aggregate activity was also elicited upon overexpression of the W383C CTSD variant, which is predominantly sequestered in the ER and consequently remains unprocessed, suggesting that proCTSD, rather than mature CTSD, serves to suppress the aggregation of the R120G αBC variant. Meanwhile, overexpression of the A58V CTSD variant, which is identical to wild-type CTSD except for the Ala58Val substitution within the pro-peptide, did not suppress the protein aggregation, indicating that the integrity of the pro-peptide is required for proCTSD to exert its anti-aggregate activity. Based on our previous finding that overexpression of the ER transmembrane protein CLN6 (ceroid-lipofuscinosis, neuronal 6), identified as an interacting protein of the ER-anchored αBC, prevents the R120G αBC variant from aggregating, the CLN6-proCTSD coupling was hypothesized to underpin the functionality of proCTSD within the ER. Indeed, CTSD, when overexpressed in CLN6-depleted cells, was unable to exert its anti-aggregate activity, supporting our view. Collectively, we show here that proCTSD prevents the protein aggregation through the functional association with CLN6 in the microenvironment surrounding the ER membrane, shedding light on a novel aspect of proCTSD and its potential involvement in CTSD-related disorders characterized by the accumulation of aberrant protein aggregates.
(徳島大学機関リポジトリ): ● Metadata: 119515
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ymgme.2024.108539
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 39032464; ● Search Scopus @ Elsevier (PMID): 39032464; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ymgme.2024.108539

(徳島大学機関リポジトリ: 119515, DOI: 10.1016/j.ymgme.2024.108539, PubMed: 39032464) Misaki Onodera, Saori Tsujimoto, Syusuke Doi, Arisa Yamashita, Tetsuo Yamazaki, Takao Makifuchi and Tetsuya Inazu :
p.Asn77Lys homozygous CLN6 mutation in two unrelated Japanese patients with Kufs disease, an adult onset neuronal ceroid lipofuscinosis.,
Clinica Chimica Acta, Vol.523, No.21, 191-195, 2021.

(要約): Gene analysis results of the first patient revealed a homozygous mutation c231C>G, p.Asn77Lys in exon 3 and a homozygous c.297+48 A>T mutation in intron 3 in the CLN6 gene. The Asn amino acid is perfectly conserved among species. In silico analysis showed that the mutation is predicted to be probably damaging. Moreover, the second patient with Kufs disease also had the same homozygous mutations. These data suggest that the missense mutation must be pathogenic. Furthermore, the patients had lived in the same district; therefore, they both potentially inherited the founder effect mutations.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.cca.2021.09.021
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34597687; ● Search Scopus @ Elsevier (PMID): 34597687; ● Search Scopus @ Elsevier (DOI): 10.1016/j.cca.2021.09.021

(DOI: 10.1016/j.cca.2021.09.021, PubMed: 34597687) Yuki Shiro, Arisa Yamashita, Kana Watanabe and Tetsuo Yamazaki :
CLN6's luminal tail-mediated functional interference between CLN6 mutants as a novel pathomechanism for the neuronal ceroid lipofuscinoses.,
Biomedical Research, Vol.42, No.4, 129-138, 2021.

(要約): CLN6 (Ceroid Lipofuscinosis, Neuronal, 6) is a 311-amino acid protein spanning the endoplasmic reticulum membrane. Mutations in CLN6 are linked to CLN6 disease, a hereditary neurodegenerative disorder categorized into the neuronal ceroid lipofuscinoses. CLN6 disease is an autosomal recessive disorder and individuals affected with this disease have two identical (homozygous) or two distinct (compound heterozygous) CLN6 mutant alleles. Little has been known about CLN6's physiological roles and the disease mechanism. We recently found that CLN6 prevents protein aggregate formation, pointing to impaired CLN6's anti-aggregate activity as a cause for the disease. To comprehensively understand the pathomechanism, overall anti-aggregate activity derived from two different CLN6 mutants needs to be investigated, considering patients compound heterozygous for CLN6 alleles. We focused on mutant combinations involving the S132CfsX18 (132fsX) prematurely terminated protein, produced from the most frequent mutation in CLN6. The 132fsX mutant nullified anti-aggregate activity of the P299L CLN6 missense mutant but not of wild-type CLN6. Wild-type CLN6's resistance to the 132fsX mutant was abolished by replacement of amino acids 297-301, including Pro297 and Pro299, with five alanine residues. Given that removal of CLN6's C-terminal fifteen amino acids 297-311 (luminal tail) did not affect the resistance, we suggested that CLN6's luminal tail, when unleashed from Pro297/299-mediated conformational constraints, is improperly positioned by the 132fsX mutant, thereby blocking the induction of anti- aggregate activity. We here reveal a novel mechanism for dissipating CLN6 mutants' residual functions, providing an explanation for the compound heterozygosity-driven pathogenesis.
(徳島大学機関リポジトリ): ● Metadata: 116174
(出版サイトへのリンク): ● Publication site (DOI): 10.2220/biomedres.42.129
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34380921; ● Search Scopus @ Elsevier (PMID): 34380921; ● Search Scopus @ Elsevier (DOI): 10.2220/biomedres.42.129

(徳島大学機関リポジトリ: 116174, DOI: 10.2220/biomedres.42.129, PubMed: 34380921) Arisa Yamashita, Yuki Shiro, Yuri Hiraki, Takatoshi Yujiri and Tetsuo Yamazaki :
Implications of graded reductions in CLN6's anti-aggregate activity for the development of the neuronal ceroid lipofuscinoses.,
Biochemical and Biophysical Research Communications, Vol.525, No.4, 883-888, 2020.

(要約): CLN6, spanning the endoplasmic reticulum membrane, is a protein of unknown function. Mutations in the CLN6 gene are linked to an autosomal recessively inherited disorder termed CLN6 disease, classified as a form of the neuronal ceroid lipofuscinoses (NCL). The pathogenesis of CLN6 disease remains poorly understood due to a lack of information about physiological roles CLN6 plays. We previously demonstrated that CLN6 has the ability to prevent protein aggregate formation, and thus hypothesized that the abrogation of CLN6's anti-aggregate activity underlies the development of CLN6 disease. To test this hypothesis, we narrowed down the region vital for CLN6's anti-aggregate activity, and subsequently investigated if pathogenic mutations within the region attenuate CLN6's anti-aggregate activity toward four aggregation-prone αB-crystallin (αBC) mutants. None of the four αBC mutants was prevented from aggregating by the Arg106ProfsX truncated CLN6 mutant, the human counterpart of the nclf mutant identified in a naturally occurring mouse model of late infantile-onset CLN6 disease. In contrast, the Arg149Cys and the Arg149His CLN6 mutants, both associated with adult-onset CLN6 disease, blocked aggregation of two out of and all of the four αBC mutants, respectively, indicating that CLN6's anti-aggregate activity is differentially modulated according to the substitution pattern at the same amino acid position. Collectively, we here propose that the graded reduction in CLN6's anti-aggregate activity governs the clinical course of late infantile- and adult-onset NCL.
(徳島大学機関リポジトリ): ● Metadata: 114612
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2020.03.019
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32171521; ● Search Scopus @ Elsevier (PMID): 32171521; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2020.03.019

(徳島大学機関リポジトリ: 114612, DOI: 10.1016/j.bbrc.2020.03.019, PubMed: 32171521) Arisa Yamashita, Yuri Hiraki and Tetsuo Yamazaki :
Identification of CLN6 as a molecular entity of endoplasmic reticulum-driven anti-aggregate activity,
Biochemical and Biophysical Research Communications, Vol.487, No.4, 917-922, 2017.

(要約): B-crystallin (BC) is a small heat shock protein. Mutations in the BC gene are linked to -crystallinopathy, a hereditary myopathy histologically characterized by intracellular accumulation of protein aggregates. The disease-causing R120G BC mutant, harboring an arginine-to-glycine replacement at position 120, is an aggregate-prone protein. We previously showed that the R120G mutant's aggregation in HeLa cells was prevented by enforced expression of BC on the endoplasmic reticulum (ER). To elucidate the molecular nature of the preventive effect on the R120G mutant, we isolated proteins binding to ER-anchored BC (TMBC). The ER transmembrane CLN6 protein was identified as a TMBC's binder. CLN6 knockdown in HeLa cells attenuated TMBC's anti-aggregate activity against the R120G mutant. Conversely, CLN6 overexpression enhanced the activity, indicating that CLN6 operates as a downstream effector of TMBC. CLN6 physically interacted with the R120G mutant, and repressed its aggregation in HeLa cells even when TMBC was not co-expressed. Furthermore, CLN6's antagonizing effect on the R120G mutant was compromised upon treatment with a lysosomal inhibitor, suggesting CLN6 requires the intact autophagy-lysosome system to prevent the R120G mutant from aggregating. We hence conclude that CLN6 is not only a molecular entity of the anti-aggregate activity conferred by the ER manipulation using TMBC, but also serves as a potential target of therapeutic interventions.
(徳島大学機関リポジトリ): ● Metadata: 111526
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2017.05.002
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28476624; ● Search Scopus @ Elsevier (PMID): 28476624; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2017.05.002

(徳島大学機関リポジトリ: 111526, DOI: 10.1016/j.bbrc.2017.05.002, PubMed: 28476624) Shin-ichiro Yamamto, Arisa Yamashita, Naokatu Arakaki, Hisao Nemoto and Tetsuo Yamazaki :
Prevention of aberrant protein aggregation by anchoring the molecular chaperone B-crystallin to the endoplasmic reticulum.,
Biochemical and Biophysical Research Communications, Vol.455, No.3-4, 241-245, 2014.

(要約): The chaperone B-crystallin (BC) is a member of the small heat shock protein family and its point or truncated mutants cause the muscular disorder -crystallinopathy. The illness is histologically characterized by accumulation of protein aggregates in muscle cells. Expression of the myopathy-causing R120G mutant of BC, harboring an arginine-to-glycine mutation at position 120, results in aggregate formation. We demonstrated that tethering BC to the endoplasmic reticulum (ER) membrane represses the protein aggregation mediated by the R120G mutant. ER-anchored BC decreased the amount of the R120G mutant through autophagic proteolysis. In contrast, knockdown of ATG5, an E3 ligase essential for autophagy, in ER-anchored BC-transfected cells restored the quantity of the R120G mutant. In this context, aggregate formation was still suppressed, indicating that ER-anchored BC profoundly constrains aggregation competency of the R120G mutant separately from downregulating the abundance of the mutant. We have proposed that protein aggregation is prevented by manipulation of the ER microenvironment with BC, and have shed light on a novel aspect of the ER as a therapeutic target.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2014.10.151
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25449278; ● Search Scopus @ Elsevier (PMID): 25449278; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2014.10.151

(DOI: 10.1016/j.bbrc.2014.10.151, PubMed: 25449278) Shin-ichiro Yamamto, Tetsuo Yamazaki, Shinji Komazaki, Takeshi Yamashita, Masako Osaki, Masaya Matsubayashi, Hiroyasu Kidoya, Nobuyuki Takakura, Daiju Yamazaki and Sho Kakizawa :
Contribution of calumin to embryogenesis through participation in the endoplasmic reticulum-associated degradation activity.,
Developmental Biology, Vol.393, No.1, 33-43, 2014.

(要約): Calumin is an endoplasmic reticulum (ER)-transmembrane protein, and little is known about its physiological roles. Here we showed that calumin homozygous mutant embryos die at embryonic days (E) 10.5-11.5. At mid-gestation, calumin was expressed predominantly in the yolk sac. Apoptosis was enhanced in calumin homozygous mutant yolk sacs at E9.5, pointing to a possible link to the embryonic lethality. Calumin co-immunoprecipitated with ERAD components such as p97, BIP, derlin-1, derlin-2 and VIMP, suggesting its involvement in ERAD. Indeed, calumin knockdown in HEK 293 cells resulted in ERAD being less efficient, as demonstrated by attenuation in both degradations of a misfolded 1-antitrypsin variant and the ER-to-cytosol dislocation of cholera toxin A1 subunit. In calumin homozygous mutant yolk sac endoderm cells, ER stress-associated alterations were observed, including lipid droplet accumulation, fragmentation of the ER and dissociation of ribosomes from the ER. In this context, the ER-overload response, assumed to be cytoprotective, was also triggered in the mutant endoderm cells, but seemed to fully counteract the excessive ER stress generated due to defective ERAD. Taken together, our findings suggested that calumin serves to maintain the yolk sac integrity through participation in the ERAD activity, contributing to embryonic development.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ydbio.2014.06.024
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25009997; ● Search Scopus @ Elsevier (PMID): 25009997; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ydbio.2014.06.024

(DOI: 10.1016/j.ydbio.2014.06.024, PubMed: 25009997) Naokatu Arakaki, Arisa Yamashita, Shingo Niimi and Tetsuo Yamazaki :
Involvement of reactive oxygen species in osteoblastic differentiation of MC3T3-E1 cells accompanied by mitochondrial morphological dynamics.,
Biomedical Research, Vol.34, No.3, 161-166, 2013.

(要約): Bone remodeling is regulated by local factors that regulate bone-forming osteoblasts and boneresorbing osteoclasts, in addition to hormonal activity. Recent studies have shown that reactive oxygen species (ROS) act as an intracellular signal mediator for osteoclast differentiation. However the role of ROS on osteoblast differentiation is poorly understood. Here, we investigated the impact of ROS on osteoblastic differentiation of MC3T3-E1 cells. Osteogenic induction resulted in notable enhancement of mineralization and expression of osteogenic marker gene alkaline phosphatase, which were accompanied by an increase in ROS production. Additionally, we found that mitochondrial morphology dynamically changed from tubular reticulum to fragmented structures during the differentiation, suggesting that mitochondrial morphological transition is a novel osteoblast differentiation index. The antioxidant N-acetyl cysteine prevented not only ROS production but also mineralization and mitochondrial fragmentation. It is therefore suggested that the ROSdependent signaling pathways play a role in osteoblast differentiation accompanied by mitochondrial morphological transition.
(出版サイトへのリンク): ● Publication site (DOI): 10.2220/biomedres.34.161
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23782750; ● Summary page in Scopus @ Elsevier: 2-s2.0-84879139579

(DOI: 10.2220/biomedres.34.161, PubMed: 23782750, Elsevier: Scopus) Arisa Yamashita, Tatsuya Taniwaki, Yuka Kaikoi and Tetsuo Yamazaki :
Protective role of the endoplasmic reticulum protein mitsugumin23 against ultraviolet C-induced cell death.,
FEBS Letters, Vol.587, No.9, 1299-1303, 2013.

(要約): The endoplasmic reticulum (ER) operates in adaptive responses to various stresses, dictating cell fate. Here we show that knockdown of the ER protein mitsugumin23 (MG23) enhances cell death induced by ultraviolet C (UVC), which causes DNA damage. The small heat shock protein B-crystallin (BC) is identified as a MG23 binding molecule and its knockdown facilitates death of UVC-exposed cells. Conversely, BC lowered UVC sensitivity when expressed as an ER-anchored form. Taken together, the results suggest that MG23 plays a protective role against UVC by accumulating BC in the close vicinity of the ER.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.febslet.2013.03.024
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23542032; ● Summary page in Scopus @ Elsevier: 2-s2.0-84876498476

(DOI: 10.1016/j.febslet.2013.03.024, PubMed: 23542032, Elsevier: Scopus) Dale Ty Troutman, Wei Hu, Stephanie Fulenchek, Tetsuo Yamazaki, Tomohiro Kurosaki, Fernando J Bazan and Chandrashekhar Pasare :
Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt.,
Proceedings of the National Academy of Sciences of the United States of America, Vol.109, No.1, 273-278, 2011.

(要約): Toll like receptors (TLRs) use Toll-IL-1 receptor (TIR) domain-containing adapters, such as myeloid differentiation primary response gene 88 (MyD88) and TIR domain-containing adapter inducing IFN- (TRIF), to induce activation of transcription factors, including NF-B, MAP kinases, and IFN regulatory factors. TLR signaling also leads to activation of PI3K, but the molecular mechanism is not understood. Here we have discovered a unique role for B-cell adapter for PI3K (BCAP) in the TLR-signaling pathway. We find that BCAP has a functional N-terminal TIR homology domain and links TLR signaling to activation of PI3K. In addition, BCAP negatively regulates proinflammatory cytokine secretion upon TLR stimulation. In vivo, the absence of BCAP leads to exaggerated recruitment of inflammatory myeloid cells following infections and enhanced susceptibility to dextran sulfate sodium-induced colitis. Our results demonstrate that BCAP is a unique TIR domain-containing TLR signaling adapter crucial for linking TLRs to PI3K activation and regulating the inflammatory response.
(出版サイトへのリンク): ● Publication site (DOI): 10.1073/pnas.1118579109
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22187460; ● Search Scopus @ Elsevier (PMID): 22187460; ● Search Scopus @ Elsevier (DOI): 10.1073/pnas.1118579109

(DOI: 10.1073/pnas.1118579109, PubMed: 22187460) Sungwon Song, Claude Chew, Benjamin M. Dale, Daniel Traum, James Peacock, Tetsuo Yamazaki, Raphael Clynes, Tomohiro Kurosaki and Steven Greenberg :
A Requirement for the p85 PI3K Adapter Protein BCAP in the Protection of Macrophages from Apoptosis Induced by Endoplasmic Reticulum Stress.,
The Journal of Immunology, Vol.187, No.2, 619-625, 2011.

(要約): Macrophages are innate immune cells that play key roles in regulation of the immune response and in tissue injury and repair. In response to specific innate immune stimuli, macrophages may exhibit signs of endoplasmic reticulum (ER) stress and progress to apoptosis. Factors that regulate macrophage survival under these conditions are poorly understood. In this study, we identified B cell adapter protein (BCAP), a p85 PI3K-binding adapter protein, in promoting survival in response to the combined challenge of LPS and ER stress. BCAP was unique among nine PI3K adapter proteins in being induced >10-fold in response to LPS. LPS-stimulated macrophages incubated with thapsigargin, a sarcoplasmic/endoplasmic reticulum calcium ATPase inhibitor that induces ER stress, underwent caspase-3 activation and apoptosis. Macrophages from BCAP(-/-) mice exhibited increased apoptosis in response to these stimuli. BCAP-deficient macrophages demonstrated decreased activation of Akt, but not ERK, and, unlike BCAP-deficient B cells, expressed normal amounts of the NF-B subunits, c-Rel and RelA. Retroviral transduction of BCAP-deficient macrophages with wild-type BCAP, but not a Y4F BCAP mutant defective in binding the SH2 domain of p85 PI3K, reversed the proapoptotic phenotype observed in BCAP-deficient macrophages. We conclude that BCAP is a nonredundant PI3K adapter protein in macrophages that is required for maximal cell survival in response to ER stress. We suggest that as macrophages engage their pathogenic targets, innate immune receptors trigger increased expression of BCAP, which endows them with the capacity to withstand further challenges from ongoing cellular insults, such as ER stress.
(出版サイトへのリンク): ● Publication site (DOI): 10.4049/jimmunol.0903425
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21685326; ● Search Scopus @ Elsevier (PMID): 21685326; ● Search Scopus @ Elsevier (DOI): 10.4049/jimmunol.0903425

(DOI: 10.4049/jimmunol.0903425, PubMed: 21685326) Kita Toshiyuki, Nishida Hana, Niimi Shingo, Hirofumi Shibata, Tetsuo Yamazaki and Naokatu Arakaki :
Role of cell surface H⁺-ATP synthase on adipocyte differentiation.,
Inflammation and Regeneration, Vol.30, No.5, 425-427, 2010.

(キーワード): cell surface H^+-ATP synthase / adipocyte differentiation / triglyceride accumulation / adipolysis / obesity
(出版サイトへのリンク): ● Publication site (DOI): 10.2492/inflammregen.30.425
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001205257545984; ● Search Scopus @ Elsevier (DOI): 10.2492/inflammregen.30.425

(DOI: 10.2492/inflammregen.30.425, CiNii: 1390001205257545984) Tetsuo Yamazaki, Nozomi Sasaki, Miyuki Nishi and Hiroshi Takeshima :
Facilitation of DNA damage-induced apoptosis by endoplasmic reticulum protein mitsugumin23.,
Biochemical and Biophysical Research Communications, Vol.392, No.2, 196-200, 2010.

(要約): The endoplasmic reticulum (ER) emanates context-dependent signals, thereby mediating cellular response to a variety of stresses. However, the underlying molecular mechanisms have been enigmatic. To better understand the signaling capacity of the ER, we focused on roles played by mitsugumin23 (MG23), a protein residing predominantly in this organelle. Overexpression of MG23 in human embryonic kidney 293T cells specifically enhanced apoptosis triggered by etoposide, a DNA-damaging anti-cancer drug. Conversely, genetic deletion of MG23 reduced susceptibility of thymocytes to DNA damage-induced apoptosis, which was demonstrated by whole-body irradiation experiments. In this setting, induction of the tumor-suppressor gene p53 was attenuated in MG23-knockout thymocytes as compared with their wild-type counterparts, consistent with the elevated radioresistance. It is therefore suggested that MG23 is an essential component of ER-generated lethal signals provoked upon DNA damage, specifying cell fate under pathophysiological conditions.
(キーワード): Animals / Antineoplastic Agents / Apoptosis / Cell Line / DNA Damage / Endoplasmic Reticulum / Etoposide / Gene Knockout Techniques / Humans / Membrane Proteins / Mice / Mice, Knockout / Radiation Tolerance / Stress, Physiological / Thymus Gland / Tumor Suppressor Protein p53
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2010.01.013
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20060811; ● Search Scopus @ Elsevier (PMID): 20060811; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2010.01.013

(DOI: 10.1016/j.bbrc.2010.01.013, PubMed: 20060811) Daiju Yamazaki, Shinji Komazaki, Hiroki Nakanishi, Aya Mishima, Miyuki Nishi, Masayuki Yazawa, Tetsuo Yamazaki, Ryo Taguchi and Hiroshi Takeshima :
Essential role of the TRIC-B channel in Ca2+ handling of alveolar epithelial cells and in perinatal lung maturation.,
Development, Vol.136, No.14, 2355-2361, 2009.

(要約): TRIC channels function as monovalent cation-specific channels that mediate counter ion movements coupled with ryanodine receptor-mediated Ca(2+) release from intracellular stores in muscle cells. Mammalian tissues differentially contain two TRIC channel subtypes: TRIC-A is abundantly expressed in excitable cells, whereas TRIC-B is ubiquitously expressed throughout tissues. Here, we report the physiological role of TRIC-B channels in mouse perinatal development. TRIC-B-knockout neonates were cyanotic owing to respiratory failure and died shortly after birth. In the mutant neonates, the deflated lungs exhibited severe histological defects, and alveolar type II epithelial cells displayed ultrastructural abnormalities. The metabolic conversion of glycogen into phospholipids was severely interrupted in the mutant type II cells, and surfactant phospholipids secreted into the alveolar space were insufficient in the mutant neonates. Moreover, the mutant type II cells were compromised for Ca(2+) release mediated by inositol-trisphosphate receptors, despite Ca(2+) overloading in intracellular stores. Our results indicate that TRIC-B channels take an active part in Ca(2+) signalling to establish specialised functions in type II cells and are thus essential for perinatal lung maturation.
(キーワード): Animals / Animals, Newborn / Calcium Signaling / Epithelial Cells / Female / Ion Channels / Lung / Mice / Mice, Inbred C57BL / Mice, Knockout / Microscopy, Electron, Transmission / Models, Biological / Phospholipids / Pregnancy / Pulmonary Alveoli
(出版サイトへのリンク): ● Publication site (DOI): 10.1242/dev.036798
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19515693; ● Search Scopus @ Elsevier (PMID): 19515693; ● Search Scopus @ Elsevier (DOI): 10.1242/dev.036798

(DOI: 10.1242/dev.036798, PubMed: 19515693) Haruko Masumiya, Yasuhide Asaumi, Miyuki Nishi, Susumu Minamisawa, Satomi Adachi-Akahane, Morikatsu Yoshida, Kenji Kangawa, Kenta Ito, Yutaka Kagaya, Teruyuki Yanagisawa, Tetsuo Yamazaki, Jianjie Ma and Hiroshi Takeshima :
Mitsugumin 53-mediated maintenance of K+ currents in cardiac myocytes.,
Channels, Vol.3, No.1, 6-11, 2009.

(要約): Mitsugumin 53 (MG53) is a muscle-specific RBCC/TRIM family member predominantly localized on small vesicles underneath the plasma membrane. Upon cell-surface lesion MG53 recruits the vesicles to the repair site in an oxidation-dependent manner and MG53-knockout mice develop progressive myopathy associated with defective membrane repair. In this report, we focus on MG53-knockout cardiomyocytes showing abnormal action potential profile and a reduced K+ current density. In cDNA expression experiments using cultured cells, KV2.1-mediated currents were remarkably increased by MG53 without affecting the total and cell-surface levels of channel expression. In imaging analysis MG53 seemed to facilitate the mobility of KV2.1-containing endocytic vesicles with acidic pH. However, similar effects on the current density and vesicular mobility were not observed in the putative dominant-negative form of MG53. Our data suggest that MG53 is involved in a constitutive cycle of certain cell-surface proteins between the plasma membrane and endosome-like vesicles in striated muscle, and also imply that the vesicular dynamics are essential for the quality control of KV2.1 in cardiomyocytes.
(キーワード): Action Potentials / Animals / Calcium Channels, L-Type / Cardiomyopathies / Carrier Proteins / Cell Membrane / Cells, Cultured / Endosomes / Humans / Hydrogen-Ion Concentration / Mice / Mice, Knockout / Mutation / Myocytes, Cardiac / カリウム (potassium) / Protein Transport / Shab Potassium Channels / Time Factors / Transfection
(出版サイトへのリンク): ● Publication site (DOI): 10.4161/chan.3.1.7571
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19202355; ● Summary page in Scopus @ Elsevier: 2-s2.0-66149106316

(DOI: 10.4161/chan.3.1.7571, PubMed: 19202355, Elsevier: Scopus) Alexander W. MacFarlane, Tetsuo Yamazaki, Min Fang, Luis J. Sigal, Tomohiro Kurosaki and Kerry S. Campbell :
Enhanced NK-cell development and function in BCAP-deficient mice.,
Blood, Vol.112, No.1, 131-140, 2008.

(要約): In B lymphocytes, the B-cell adaptor for phosphatidylinositol 3-kinase (BCAP) facilitates signaling from the antigen receptor. Mice lacking BCAP have a predominantly immature pool of B cells with impaired immune function and increased susceptibility to apoptosis. Unexpectedly, we have found that natural killer (NK) cells from BCAP-deficient mice are more mature, more long-lived, more resistant to apoptosis, and exhibit enhanced functional activity compared with NK cells from wild-type mice. Surprisingly, these effects are evident despite a severe impairment of the immunoreceptor tyrosine-based activation motif-mediated Akt signaling pathway. The seemingly paradoxical phenotype reveals inherent differences in the signals controlling the final maturation of B cells and NK cells, which depend on positive and negative signals, respectively. Both enhanced interferon-gamma responses and augmented maturation of NK cells in BCAP-deficient mice are independent of available MHC class I ligands. Our data support a model in which blunting of BCAP-mediated activation signaling in developing NK cells promotes functionality, terminal maturation, and long-term survival.
(キーワード): 1-Phosphatidylinositol 3-Kinase / Adaptor Proteins, Signal Transducing / Animals / Apoptosis / Cell Aging / Cell Differentiation / Cytotoxicity, Immunologic / Female / Humans / Interferon-gamma / Killer Cells, Natural / Male / Mice / Mice, Congenic / Mice, Inbred C57BL / Mice, Knockout / Models, Immunological / Proto-Oncogene Proteins c-akt / Self Tolerance / Signal Transduction
(出版サイトへのリンク): ● Publication site (DOI): 10.1182/blood-2007-08-107847
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18337558; ● Search Scopus @ Elsevier (PMID): 18337558; ● Search Scopus @ Elsevier (DOI): 10.1182/blood-2007-08-107847

(DOI: 10.1182/blood-2007-08-107847, PubMed: 18337558) Yuichi Aiba, Megumi Kameyama, Tetsuo Yamazaki, Thomas F. Tedder and Tomohiro Kurosaki :
Regulation of B-cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase.,
Blood, Vol.111, No.3, 1497-1503, 2007.

(要約): Despite the importance of phosphoinositide 3-kinase (PI3K) in B-cell development, its activation mechanism still remains elusive. In this study, we show that deletion of both BCAP and CD19 leads to an almost complete block of BCR-mediated Akt activation and to severe defects in generation of immature and mature B cells. The YXXM motifs in BCAP and CD19 are crucial for regulating B-cell development in that mutation of these motifs abrogated their ability to induce BCR-mediated Akt activation as well as to promote B-cell development. Furthermore, the developmental defect in CD19(-/-)BCAP(-/-) B cells was partly relieved by introducing a constitutively active form of PI3K or PDK1. Together, our data suggest that BCAP and CD19 have complementary roles in BCR-mediated PI3K activation, thereby, at least in part, contributing to B-cell development.
(キーワード): 1-Phosphatidylinositol 3-Kinase / Adaptor Proteins, Signal Transducing / Animals / Antigens, CD19 / B-Lymphocytes / Cell Differentiation / Enzyme Activation / Mice / Mice, Knockout / Protein Binding / Protein-Serine-Threonine Kinases / Proto-Oncogene Proteins c-akt / Signal Transduction
(出版サイトへのリンク): ● Publication site (DOI): 10.1182/blood-2007-08-109769
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18025150; ● Search Scopus @ Elsevier (PMID): 18025150; ● Search Scopus @ Elsevier (DOI): 10.1182/blood-2007-08-109769

(DOI: 10.1182/blood-2007-08-109769, PubMed: 18025150) Atsushi Ikeda, Taisuke Miyazaki, Sho Kakizawa, Yasushi Okuno, Soken Tsuchiya, Akira Myomoto, Shin-ya Saito, Tetsuji Yamamoto, Tetsuo Yamazaki, Masamitsu Iino, Gozoh Tsujimoto, Masahiko Watanabe and Hiroshi Takeshima :
Abnormal features in mutant cerebellar Purkinje cells lacking junctophilins.,
Biochemical and Biophysical Research Communications, Vol.363, No.3, 835-839, 2007.

(要約): Junctional membrane complexes (JMCs) generated by junctophilins are required for Ca(2+)-mediated communication between cell-surface and intracellular channels in excitable cells. Knockout mice lacking neural junctophilins (JP-DKO) show severe motor defects and irregular cerebellar plasticity due to abolished channel crosstalk in Purkinje cells (PCs). To precisely understand aberrations in JP-DKO mice, we further analyzed the mutant PCs. During the induction of cerebellar plasticity via electrical stimuli, JP-DKO PCs showed insufficient depolarizing responses. Immunochemistry detected mild impairment in synaptic maturation and hyperphosphorylation of protein kinase Cgamma in JP-DKO PCs. Moreover, gene expression was slightly altered in the JP-DKO cerebellum. Therefore, the mutant PCs bear marginal but widespread abnormalities, all of which likely cause cerebellar motor defects in JP-DKO mice.
(キーワード): Action Potentials / Animals / Calcium / Cerebellum / Electric Stimulation / Gene Expression Profiling / Immunoblotting / Membrane Proteins / Mice / Mice, Knockout / Mutation / Oligonucleotide Array Sequence Analysis / Phosphorylation / Protein Kinase C / Purkinje Cells
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2007.09.062
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17904530; ● Search Scopus @ Elsevier (PMID): 17904530; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2007.09.062

(DOI: 10.1016/j.bbrc.2007.09.062, PubMed: 17904530) Tetsuo Yamazaki, Nozomi Sasaki, Miyuki Nishi, Daiju Yamazaki, Atsushi Ikeda, Yasushi Okuno, Shinji Komazaki and Hiroshi Takeshima :
Augmentation of drug-induced cell death by ER protein BRI3BP.,
Biochemical and Biophysical Research Communications, Vol.362, No.4, 971-975, 2007.

(要約): To determine the contribution of the endoplasmic reticulum (ER) to cell fate decision, we focused on BRI3-binding protein (BRI3BP) residing in this organelle. BRI3BP, when overexpressed, augmented the apoptosis of human embryonic kidney 293T cells challenged with drugs including the anti-cancer agent etoposide. In contrast, the knockdown of BRI3BP reduced the drug-triggered apoptosis. BRI3BP overexpression enhanced both mitochondrial cytochrome c release and caspase-3 activity in etoposide-treated cells. In response to etoposide, the ER reorganized into irregularly shaped lamellae in mock-transfected cells, whereas in BRI3BP-overexpressing cells, such reorganization was not observed. These observations suggest that BRI3BP is involved in the structural dynamics of the ER and affects mitochondrial viability. Taken together, BRI3BP, widely expressed in animal cell types, seems to possess a pro-apoptotic property and can potentiate drug-induced apoptosis.
(キーワード): Antineoplastic Agents / Apoptosis / Carrier Proteins / Cell Line / Dose-Response Relationship, Drug / Drug Synergism / Endoplasmic Reticulum / Etoposide / Humans / Kidney / Mitochondria
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2007.08.082
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17765869; ● Search Scopus @ Elsevier (PMID): 17765869; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2007.08.082

(DOI: 10.1016/j.bbrc.2007.08.082, PubMed: 17765869) Miao Zhang, Tetsuo Yamazaki, Masayuki Yazawa, Susan Treves, Miyuki Nishi, Machiko Murai, Eisuke Shibata, Francesco Zorzato and Hiroshi Takeshima :
Calumin, a novel Ca2+-binding transmembrane protein on the endoplasmic reticulum.,
Cell Calcium, Vol.42, No.1, 83-90, 2007.

(要約): We have identified a novel endoplasmic reticulum (ER)-resident protein, named "calumin", which is expressed in various tissues. This protein has a molecular mass of approximately 60 kDa and is composed of an ER-luminal domain rich in acidic residues, a single transmembrane segment, and a large cytoplasmic domain. Biochemical experiments demonstrated that the amino-terminal luminal domain is capable of binding Ca2+ with a high capacity and moderate affinity. In embryonic fibroblasts derived from calumin-knockout mice exhibiting embryonic and neonatal lethality, fluorometric Ca2+ imaging detected insufficient Ca2+ contents in intracellular stores and attenuated store-operated Ca2+ entry. Moreover, the mutant fibroblasts were highly sensitive to cell death induced by ER stress. These observations suggest that calumin plays an essential role in ER Ca2+ handling and is also implicated in signaling from the ER, which is closely associated with cell-fate decision.
(キーワード): Animals / Calcium / Calcium Signaling / Calcium-Binding Proteins / Cloning, Molecular / Endoplasmic Reticulum / Membrane Proteins / Mice / Mice, Knockout / Molecular Weight / Oxidative Stress / Rats / Thapsigargin / Tunicamycin
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ceca.2006.11.009
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17204322; ● Search Scopus @ Elsevier (PMID): 17204322; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ceca.2006.11.009

(DOI: 10.1016/j.ceca.2006.11.009, PubMed: 17204322) Yuichi Aiba, Tetsuo Yamazaki, Takaharu Okada, Kumiko Gotoh, Hideki Sanjo, Masato Ogata and Tomohiro Kurosaki :
BANK negatively regulates Akt activation and subsequent B cell responses.,
Immunity, Vol.24, No.3, 259-268, 2006.

(要約): BANK is an adaptor protein that is highly expressed in B cells. To investigate its physiological role, we generated BANK-deficient mice. BANK-deficient mice displayed enhanced germinal center formation and IgM production in response to T-dependent antigens, whereas this phenotype was blocked in CD40-BANK double knockout mice. Involvement of BANK in CD40 signaling was further demonstrated by in vitro analysis. CD40-mediated proliferation and survival were significantly increased in BANK-deficient B cells, with enhanced Akt activation, whereas introduction of dominant-negative Akt into BANK-deficient B cells suppressed the augmented CD40-mediated responses. Together, our findings suggest that BANK attenuates CD40-mediated Akt activation, thereby preventing hyperactive B cell responses.
(キーワード): 1-Phosphatidylinositol 3-Kinase / Adaptor Proteins, Signal Transducing / Animals / Antigens, CD40 / B-Lymphocytes / Cells, Cultured / Lymphocyte Activation / Mice / Proto-Oncogene Proteins c-akt / Signal Transduction
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.immuni.2006.01.002
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16546095; ● Search Scopus @ Elsevier (PMID): 16546095; ● Search Scopus @ Elsevier (DOI): 10.1016/j.immuni.2006.01.002

(DOI: 10.1016/j.immuni.2006.01.002, PubMed: 16546095) Tetsuo Yamazaki and Tomohiro Kurosaki :
Contribution of BCAP to maintenance of mature B cells through c-Rel.,
Nature Immunology, Vol.4, No.8, 780-786, 2003.

(要約): Mice deficient in the B cell adaptor for phosphoinositide 3-kinase (BCAP) have reduced numbers of mature B lymphocytes, which show defects in cell survival and proliferation. We found here that the NF-kappa B (Rel) pathway was impaired in BCAP-deficient mature B cells and that NF-kappa B target genes, indispensable for cell survival and division, were not induced in response to B cell receptor (BCR) stimulation. Among the NF-kappa B (Rel) family, expression of c-Rel was specifically reduced in BCAP-deficient B cells. Retrovirus-mediated reintroduction of c-Rel restored the pool size of immunoglobulin (Ig)M(lo)IgD(hi) mature B cells in the spleen as well as proliferative responses to BCR stimulation. These results indicate BCAP is essential in the maintenance of mature B cells through functional coupling with c-Rel.
(キーワード): Adaptor Proteins, Signal Transducing / Animals / B-Lymphocytes / Carrier Proteins / Mice / NF-kappa B / Proto-Oncogene Proteins c-rel
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/ni949
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12833156; ● Search Scopus @ Elsevier (PMID): 12833156; ● Search Scopus @ Elsevier (DOI): 10.1038/ni949

(DOI: 10.1038/ni949, PubMed: 12833156) Stephen C. Bunnell, David I. Hong, Julia R. Kardon, Tetsuo Yamazaki, C Jane McGlade, Valarie A. Barr and Lawrence E. Samelson :
T cell receptor ligation induces the formation of dynamically regulated signaling assemblies.,
The Journal of Cell Biology, Vol.158, No.7, 1263-1275, 2002.

(要約): Tcell antigen receptor (TCR) ligation initiates tyrosine kinase activation, signaling complex assembly, and immune synapse formation. Here, we studied the kinetics and mechanics of signaling complex formation in live Jurkat leukemic T cells using signaling proteins fluorescently tagged with variants of enhanced GFP (EGFP). Within seconds of contacting coverslips coated with stimulatory antibodies, T cells developed small, dynamically regulated clusters which were enriched in the TCR, phosphotyrosine, ZAP-70, LAT, Grb2, Gads, and SLP-76, excluded the lipid raft marker enhanced yellow fluorescent protein-GPI, and were competent to induce calcium elevations. LAT, Grb2, and Gads were transiently associated with the TCR. Although ZAP-70-containing clusters persisted for more than 20 min, photobleaching studies revealed that ZAP-70 continuously dissociated from and returned to these complexes. Strikingly, SLP-76 translocated to a perinuclear structure after clustering with the TCR. Our results emphasize the dynamically changing composition of signaling complexes and indicate that these complexes can form within seconds of TCR engagement, in the absence of either lipid raft aggregation or the formation of a central TCR-rich cluster.
(キーワード): Actins / Adaptor Proteins, Signal Transducing / Antigens, CD3 / Calcium / Cholesterol / Green Fluorescent Proteins / Humans / Jurkat Cells / Luminescent Proteins / Membrane Lipids / Membrane Microdomains / Membrane Proteins / Microscopy, Confocal / Palmitic Acid / Phosphoproteins / Protein Binding / Protein Processing, Post-Translational / Protein-Tyrosine Kinases / Receptors, Antigen, T-Cell / Signal Transduction / T-Lymphocytes / ZAP-70 Protein-Tyrosine Kinase
(出版サイトへのリンク): ● Publication site (DOI): 10.1083/jcb.200203043
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12356870; ● Search Scopus @ Elsevier (PMID): 12356870; ● Search Scopus @ Elsevier (DOI): 10.1083/jcb.200203043

(DOI: 10.1083/jcb.200203043, PubMed: 12356870) Tetsuo Yamazaki, Kristien Zaal, Dale Hailey, John Presley, Jennifer Lippincott-Schwartz and Lawrence E. Samelson :
Role of Grb2 in EGF-stimulated EGFR internalization.,
Journal of Cell Science, Vol.115, No.Pt 9, 1791-1802, 2002.

(要約): Grb2 is an adaptor molecule that couples membrane receptors such as the epidermal growth factor receptor (EGFR) to intracellular signaling pathways. To gain insight into the trafficking pathways followed by these molecules after activation by EGF, we visualized Grb2 and EGFR fused to GFP spectral variants in single live cells. In nonstimulated cells, Grb2-YFP was primarily localized diffusely in the cytoplasm, whereas EGFR-CFP was found on the plasma membrane and in endocytic structures localized in the perinuclear area. Within 1 minute of EGF stimulation, Grb2 redistributed to the plasma membrane where it bound EGFR-CFP in an SH2 dependent manner. The plasma membrane then began to dynamically ruffle, and Grb2-YFP and EGFR-CFP were found to internalize together in large macropinocytic structures. These structures were morphologically distinct from conventional, clathrin-derived endosomes and did not label with transferrin, AP-2 or clathrin heavy chain. Evidence that these structures did not require clathrin for internalization came from experiments showing that expression of the C-terminus of AP-180, which inhibited transferrin uptake, had no effect on EGF-induced internalization of EGFR. YFP-tagged Grb2 containing an inhibitory mutation in either N- or C-SH3 domain redistributed to the plasma membrane upon EGF stimulation, but the macropinocytic structures containing Grb2-YFP and EGFR-CFP did not translocate inward and appeared to remain tethered to the plasma membrane. This suggested that the Grb2 SH3 domain was responsible for coupling the membranes containing EGFR with downstream effectors involved in internalization of these membranes. Transferrin uptake was unaffected in the presence of all of the SH3 domain mutants, consistent with the EGF-stimulated EGFR internalization pathway being clathrin-independent. These results demonstrate a role for Grb2 in events associated with a macropinocytic internalization pathway for EGFR in activated cells.
(キーワード): Adaptor Protein Complex 2 / Adaptor Proteins, Signal Transducing / Animals / COS Cells / Cell Membrane / Clathrin / Dynamins / Endocytosis / Epidermal Growth Factor / Eukaryotic Cells / GRB2 Adaptor Protein / Intracellular Membranes / Protein Binding / Protein Structure, Tertiary / Protein Transport / Proteins / Receptor, Epidermal Growth Factor / Recombinant Fusion Proteins / Transferrin / Transport Vesicles
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11956311; ● Search Scopus @ Elsevier (PMID): 11956311

(PubMed: 11956311) Tetsuo Yamazaki, Kiyoshi Takeda, Kumiko Gotoh, Hiroshi Takeshima, Shizuo Akira and Tomohiro Kurosaki :
Essential immunoregulatory role for BCAP in B cell development and function.,
The Journal of Experimental Medicine, Vol.195, No.5, 535-545, 2002.

(要約): BCAP was recently cloned as a binding molecule to phosphoinositide 3-kinase (PI3K). To investigate the role of BCAP, mutant mice deficient in BCAP were generated. While BCAP-deficient mice are viable, they have decreased numbers of mature B cells and B1 B cell deficiency. The mice produce lower titers of serum immunoglobulin (Ig)M and IgG3, and mount attenuated responses to T cell--independent type II antigen. Upon B cell receptor cross-linking, BCAP-deficient B cells exhibit reduced Ca(2+) mobilization and poor proliferative responses. These findings demonstrate that BCAP plays a pivotal immunoregulatory role in B cell development and humoral immune responses.
(キーワード): 1-Phosphatidylinositol 3-Kinase / Adaptor Proteins, Signal Transducing / Animals / Antibody Formation / B-Lymphocytes / Calcium / Carrier Proteins / Isoenzymes / Mice / Mice, Knockout / Phospholipase C gamma / Receptors, Antigen, B-Cell / Type C Phospholipases
(出版サイトへのリンク): ● Publication site (DOI): 10.1084/jem.20011751
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11877477; ● Summary page in Scopus @ Elsevier: 2-s2.0-0037018096

(DOI: 10.1084/jem.20011751, PubMed: 11877477, Elsevier: Scopus) Tetsuo Yamazaki, Y Hamano, H Tashiro, K Itoh, H Nakano, S Miyatake and T Saito :
CAST, a novel CD3epsilon-binding protein transducing activation signal for interleukin-2 production in T cells.,
The Journal of Biological Chemistry, Vol.274, No.26, 18173-18180, 1999.

(要約): Antigen recognition through T cell receptor (TCR)-CD3 complex transduces signals into T cells, which regulate activation, function, and differentiation of T cells. The TCR-CD3 complex is composed of two signaling modules represented by CD3zeta and CD3epsilon. Signaling through CD3zeta has been extensively analyzed, but that via CD3epsilon, which is also crucial in immature thymocyte development, is still not clearly understood. We isolated cDNA encoding a novel CD3epsilon-binding protein CAST. CAST specifically interacts in vivo and in vitro with CD3epsilon but not with CD3zeta or FcRgamma via a unique membrane-proximal region of CD3epsilon. CAST is composed of 512 amino acids including a single tyrosine and undergoes tyrosine phosphorylation upon TCR stimulation. Overexpression of two dominant-negative types of CAST, a minimum CD3epsilon-binding domain and a tyrosine-mutant, strongly suppressed NFAT activation and interleukin-2 production. These results demonstrate that CAST serves as a component of preformed TCR complex and transduces activation signals upon TCR stimulation and represents a new signaling pathway via the CD3epsilon-containing TCR signaling module.
(キーワード): Amino Acid Sequence / Animals / Antigens, CD3 / Binding Sites / Carrier Proteins / DNA, Complementary / Humans / Interleukin-2 / Intracellular Signaling Peptides and Proteins / Jurkat Cells / Mice / Molecular Sequence Data / Phosphorylation / Receptors, Antigen, T-Cell / Signal Transduction / T-Lymphocytes / Transcriptional Activation / Tumor Cells, Cultured / Tyrosine
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10373416; ● Search Scopus @ Elsevier (PMID): 10373416

(PubMed: 10373416) E L Samelson, C S Bunnell, P R Trible, Tetsuo Yamazaki and W Zhang :
Studies on the adapter molecule LAT.,
Cold Spring Harbor Symposia on Quantitative Biology, Vol.64, 259-263, 1999.

(キーワード): Adaptor Proteins, Signal Transducing / Animals / Binding Sites / Carrier Proteins / Cell Line / Humans / Ligands / Membrane Proteins / Mice / Mice, Knockout / Phosphoproteins / Protein-Tyrosine Kinases / Receptors, Antigen, T-Cell / Signal Transduction / T-Lymphocytes
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11232294; ● Search Scopus @ Elsevier (PMID): 11232294

(PubMed: 11232294) J Sloan-Lancaster, J Presley, J Ellenberg, Tetsuo Yamazaki, J Lippincott-Schwartz and E L Samelson :
ZAP-70 association with T cell receptor zeta (TCRzeta): fluorescence imaging of dynamic changes upon cellular stimulation.,
The Journal of Cell Biology, Vol.143, No.3, 613-624, 1998.

(要約): The nonreceptor protein tyrosine kinase ZAP-70 is a critical enzyme required for successful T lymphocyte activation. After antigenic stimulation, ZAP-70 rapidly associates with T cell receptor (TCR) subunits. The kinetics of its translocation to the cell surface, the properties of its specific interaction with the TCRzeta chain expressed as a chimeric protein (TTzeta and Tzetazeta), and its mobility in different intracellular compartments were studied in individual live HeLa cells, using ZAP-70 and Tzetazeta fused to green fluorescent protein (ZAP-70 GFP and Tzetazeta-GFP, respectively). Time-lapse imaging using confocal microscopy indicated that the activation-induced redistribution of ZAP-70 to the plasma membrane, after a delayed onset, is of long duration. The presence of the TCRzeta chain is critical for the redistribution, which is enhanced when an active form of the protein tyrosine kinase Lck is coexpressed. Binding specificity to TTzeta was indicated using mutant ZAP-70 GFPs and a truncated zeta chimera. Photobleaching techniques revealed that ZAP-70 GFP has decreased mobility at the plasma membrane, in contrast to its rapid mobility in the cytosol and nucleus. Tzetazeta- GFP is relatively immobile, while peripherally located ZAP-70 in stimulated cells is less mobile than cytosolic ZAP-70 in unstimulated cells, a phenotype confirmed by determining the respective diffusion constants. Examination of the specific molecular association of signaling proteins using these approaches has provided new insights into the TCRzeta-ZAP-70 interaction and will be a powerful tool for continuing studies of lymphocyte activation.
(キーワード): Actins / Cell Membrane / Cytoskeleton / Cytosol / Gene Expression / Green Fluorescent Proteins / HeLa Cells / Humans / Image Processing, Computer-Assisted / Indicators and Reagents / Luminescent Proteins / Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Membrane Proteins / Microtubules / Protein-Tyrosine Kinases / Receptors, Antigen, T-Cell / Recombinant Fusion Proteins / Vanadates / ZAP-70 Protein-Tyrosine Kinase
(出版サイトへのリンク): ● Publication site (DOI): 10.1083/jcb.143.3.613
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9813084; ● Search Scopus @ Elsevier (PMID): 9813084; ● Search Scopus @ Elsevier (DOI): 10.1083/jcb.143.3.613

(DOI: 10.1083/jcb.143.3.613, PubMed: 9813084) Y S Park, S Ueda, H Ohno, Y Hamano, M Tanaka, T Shiratori, Tetsuo Yamazaki, H Arase, N Arase, A Karasawa, S Sato, B Ledermann, Y Kondo, K Okumura, C Ra and T Saito :
Resistance of Fc receptor- deficient mice to fatal glomerulonephritis.,
The Journal of Clinical Investigation, Vol.102, No.6, 1229-1238, 1998.

(要約): Immune complex-mediated inflammation is a common mechanism of various autoimmune diseases. Glomerulonephritis (GN) is one of these diseases, and the main mechanism of the induction of GN has been unclear. We examined the contribution of Fc receptors in the induction of nephrotoxic GN by establishing and analyzing mice deficient in the Fc receptor gamma chain (FcRgamma). Whereas all wild-type mice died from severe glomerulonephritis with hypernitremia by administration of anti-glomerular basement membrane (GBM) antibodies, all FcRgamma-deficient mice survived. Histologically, wild-type mice showed glomerular hypercellularity and thrombotic changes, whereas the renal tissue in FcRgamma-deficient mice was almost intact. Deposition of anti-GBM antibody as well as complement components in the GBM were equally observed in both wild-type and knockout mice. These results demonstrate that the triggering of this type of glomerulonephritis is completely dependent on FcR+ cells.
(キーワード): Animals / Anti-Glomerular Basement Membrane Disease / Antigen-Antibody Complex / Creatinine / Disease Models, Animal / Female / Kidney Glomerulus / Macrophages / Male / Mice / Mice, Inbred C57BL / Mice, Knockout / Phagocytosis / Receptors, IgG / Sex Factors / Urea
(出版サイトへのリンク): ● Publication site (DOI): 10.1172/JCI3256
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9739057; ● Search Scopus @ Elsevier (PMID): 9739057; ● Search Scopus @ Elsevier (DOI): 10.1172/JCI3256

(DOI: 10.1172/JCI3256, PubMed: 9739057) Tetsuo Yamazaki, H Arase, S Ono, H Ohno, H Watanabe and T Saito :
A shift from negative to positive selection of autoreactive T cells by the reduced level of TCR signal in TCR-transgenic CD3 zeta-deficient mice.,
The Journal of Immunology, Vol.158, No.4, 1634-1640, 1997.

(要約): T cell selection is thought to be determined through the interaction between TCR and Ag/MHC. However, the contribution of the level of TCR signal to thymic selection remains unclear. To address this issue, we analyzed T cell selection of male Ag (HY)-specific TCR transgenic (HYTg) mice crossed with CD3 zeta-deficient (zeta KO) mice (HYTg/zeta KO), which have impaired signaling through TCR. In male HYTg/zeta KO mice, the number of thymocytes was comparable to that in normal mice, and almost all the peripheral T cells were HY specific, although these positively selected cells were anergic to male Ag. From these observations, the decrease in TCR signaling by CD3 zeta deficiency resulted in both the avoidance of negative selection and the acquisition of positive selection of autoreactive T cells in male HYTg/zeta KO mice. There was a shift of T cell selection from positive to no selection of HY-specific T cells in female HYTg/zeta KO mice also. Collectively, these findings suggest that the level of TCR signal directly regulates T cell selection; furthermore, the findings have integrated the models of T cell selection into a concept based on the quantity of TCR signal.
(キーワード): Animals / Antigens, CD8 / Autoantigens / Cell Differentiation / Clonal Anergy / Female / H-Y Antigen / Lymphocyte Activation / Male / Membrane Proteins / Mice / Mice, Inbred C57BL / Mice, Transgenic / Receptors, Antigen, T-Cell / Signal Transduction / Spleen / T-Lymphocytes / Thymus Gland
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9029099; ● Search Scopus @ Elsevier (PMID): 9029099

(PubMed: 9029099) H Nakano, Tetsuo Yamazaki, S Miyatake, N Nozaki, A Kikuchi and T Saito :
Specific interaction of topoisomerase II beta and the CD3 epsilon chain of the T cell receptor complex.,
The Journal of Biological Chemistry, Vol.271, No.11, 6483-6489, 1996.

(要約): T cell antigen receptor (TCR)-CD3 complex is composed of six different subunits: TCR alpha and TCR beta and CD3 gamma, CD3 delta, CD3 epsilon, and CD3 eta. Antigen recognition signals are transduced from TCR to the cytoplasm through the cytoplasmic domain of the CD3 chains. To understand the downstream signal transduction pathways, we cloned genes encoding proteins capable of binding to CD3 epsilon with a probe of glutathione S-transferase fused to the cytoplasmic region of CD3 epsilon. One of these clones was found to encode topoisomerase II beta (topoII beta). The binding region of CD3 epsilon is located within the N-terminal 12 amino acids containing the motif of a basic amino acid cluster. A similar motif was found in the gamma chain of Fc receptors (FcR gamma) but not in the CD33 eta chain, and indeed, FcR gamma but not CD3 eta bound to topoII beta. The binding region of topoII beta was determined to be the C terminus. Since this region appears to be the regulatory region of the enzymatic activity, the binding of CD3 epsilon might affect the function of topoII beta. Although topoII beta is localized mainly in the nucleus and CD3E is a membrane protein, we demonstrated the presence of CD3 epsilon in the nuclear fraction of thymocytes, which increased upon T cell activation. The specific interaction in cells was evidenced by co-immunoprecipitation of topoII beta and CD3E from the nuclear fraction of T cells. The possible function of this interaction is discussed.
(キーワード): Amino Acid Sequence / Animals / Base Sequence / Binding Sites / Cloning, Molecular / DNA Primers / DNA Topoisomerases, Type II / DNA, Complementary / Molecular Sequence Data / Molecular Structure / Rats / Receptor-CD3 Complex, Antigen, T-Cell / Recombinant Fusion Proteins / Sequence Homology, Amino Acid / Signal Transduction / T-Lymphocytes
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8626450; ● Search Scopus @ Elsevier (PMID): 8626450

(PubMed: 8626450) S Miyatake, H Nakano, Y S Park, Tetsuo Yamazaki, K Takase, H Matsushime, A Kato and T Saito :
Induction of G1 arrest by down-regulation of cyclin D3 in T cell hybridomas.,
The Journal of Experimental Medicine, Vol.182, No.2, 401-408, 1995.

(要約): The relationship between activation-induced growth inhibition and regulation of the cell cycle progression was investigated in T cell hybridomas by studying the function of the cell cycle-regulating genes such as G1 cyclins and their associated kinases. Activation of T cell hybridomas by anti-T cell receptor antibody induces growth arrest at G1 phase of the cell cycle and subsequently results in activation-driven cell death. Rapid reduction of both messenger RNA and protein level of the cyclin D3 is accompanied by growth arrest upon activation. Although the residual cyclin D3 protein forms a complex with cdk4 protein, cyclin D3-dependent kinase activity is severely impaired. Stable transfectants engineered to express cyclin D3 override the growth arrest upon activation. These results imply that the activation signal through T cell receptor induces the down-regulation of cyclin D3 expression and cyclin D3-dependent kinase activity, leading to growth arrest in G1 phase of the cell cycle in T cells.
(キーワード): Animals / Base Sequence / CDC2-CDC28 Kinases / Cell Cycle / Cell Death / Cyclin D2 / Cyclin D3 / Cyclin-Dependent Kinase 2 / Cyclin-Dependent Kinase 4 / Cyclin-Dependent Kinases / Cyclins / DNA Primers / Hybridomas / Lymphocyte Activation / Mice / Molecular Sequence Data / Protein-Serine-Threonine Kinases / Proto-Oncogene Proteins / Receptors, Antigen, T-Cell / Signal Transduction / T-Lymphocytes
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 7629502; ● Search Scopus @ Elsevier (PMID): 7629502

(PubMed: 7629502) H Nakano, Tetsuo Yamazaki, M Ikeda, H Masai, S Miyatake and T Saito :
Purification of glutathione S-transferase fusion proteins as a non-degraded form by using a protease-negative E. coli strain, AD202.,
Nucleic Acids Research, Vol.22, No.3, 543-544, 1994.

(キーワード): Endopeptidases / Escherichia coli / Glutathione Transferase / Recombinant Fusion Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1093/nar/22.3.543
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8127699; ● Search Scopus @ Elsevier (PMID): 8127699; ● Search Scopus @ Elsevier (DOI): 10.1093/nar/22.3.543

(DOI: 10.1093/nar/22.3.543, PubMed: 8127699)

MISC

Yuki Shiro and Tetsuo Yamazaki :
CTSD integrity in the endoplasmic reticulum is required for CLN6's anti-aggregate activity,
Molecular Genetics and Metabolism, Vol.141, No.2, 108044, 2024.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ymgme.2023.108044
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.ymgme.2023.108044

(DOI: 10.1016/j.ymgme.2023.108044) Yuki Shiro and Tetsuo Yamazaki :
Novel insight into the compound heterozygosity-driven CLN6 disease pathomechanism,
Molecular Genetics and Metabolism, Vol.135, No.2, S112, 2022.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ymgme.2021.11.297
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.ymgme.2021.11.297

(DOI: 10.1016/j.ymgme.2021.11.297)

総説・解説

髙田信二郎, 森脇好乃美, 森脇笙, 馬渕勝, 岩田織江, 国重裕二, 澤田侑樹, 吉兼麻木子, 宮崎達志, 近藤梨恵子, 渡邊典子, 山﨑哲男 :
運動療法とロボティクスの動向―近未来予測―. 筋ジストロフィーの診療・リハビリテーション医療の動向,
Journal of Clinical Rehabilitation, Vol.31, No.2, 134-142, 2022年1月.

(キーワード): 筋ジストロフィー / 運動療法 / ロボティクス / サイバネティック・アバター / キンジストロフィー / ウンドウリョウホウ / サイバネティック・アバター
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1520294429647353216

(CiNii: 1520294429647353216) 髙田信二郎, 森脇笙, 上田由佳, 元木由美, 森脇好乃美, 山﨑哲男, 田村英司, 住友祐介, 柿本直子, 海部忍 :
大腿骨近位部骨折回避のための転倒予防の重要性と具体策 : サルコペニアとフレイルからのアプローチを含む (第47回日本股関節学会学術集会シンポジウム2 大腿骨近位部骨折の予防と治療における新たな知見と進歩を目指して),
日本骨粗鬆症学会雑誌, Vol.7, No.2, 358-363, 2021年2月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1523951030943292672

(CiNii: 1523951030943292672) Daiju Yamazaki, 山﨑哲男, Hiroshi Takeshima :
TRICチャネルの生理的機能,
生化学, Vol.81, No.11, 1004-1008, 2009年11月.

(キーワード): Animals / カルシウム (calcium) / Cytoplasm / Inositol 1,4,5-Trisphosphate Receptors / Ion Channels / ノックアウトマウス (knockout mice) / Ryanodine Receptor Calcium Release Channel
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19999584; ● CiNii @ 国立情報学研究所 (CRID): 1520009407923877120; ● Search Scopus @ Elsevier (PMID): 19999584

(PubMed: 19999584, CiNii: 1520009407923877120) Daiju Yamazaki, Tetsuo Yamazaki and Hiroshi Takeshima :
New molecular components supporting ryanodine receptor-mediated Ca(2+) release: roles of junctophilin and TRIC channel in embryonic cardiomyocytes.,
Pharmacology & Therapeutics, Vol.121, No.3, 265-272, Dec. 2008.

(要約): Ca(2+) mobilization from intracellular stores is mediated by Ca(2+) release channels, designated ryanodine and IP(3) receptors, and directly regulates important cellular reactions including muscle contraction, endo/exocrine secretion, and neural excitability. In order to function as an intracellular store, the endo/sarcoplasmic reticulum is equipped with cooperative Ca(2+) uptake, storage and release machineries, comprising synergic collaborations among integral-membrane, cytoplasmic and luminal proteins. Our recent studies have demonstrated that junctophilins form junctional membrane complexes between the plasma membrane and the endo/sarcoplasmic reticulum in excitable cells, and that TRIC (trimeric intracellular cation) channels act as novel monovalent cation-specific channels on intracellular membrane systems. Knockout mice have provided evidence that both junctophilins and TRIC channels support efficient ryanodine receptor-mediated Ca(2+) release in muscle cells. This review focuses on cardiac Ca(2+) release by discussing pathological defects of mutant cardiomyocytes lacking ryanodine receptors, junctophilins, or TRIC channels.
(キーワード): Animals / Calcium / Cell Membrane / Embryo, Mammalian / Endoplasmic Reticulum / Ion Channels / Membrane Proteins / Mice / Mice, Knockout / Myocytes, Cardiac / Ryanodine Receptor Calcium Release Channel / Sarcoplasmic Reticulum
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.pharmthera.2008.11.004
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19095005; ● Search Scopus @ Elsevier (PMID): 19095005; ● Search Scopus @ Elsevier (DOI): 10.1016/j.pharmthera.2008.11.004

(DOI: 10.1016/j.pharmthera.2008.11.004, PubMed: 19095005) 池田篤史, 山﨑哲男, 竹島浩 :
リアノジン受容体による小胞体Ca[2+]放出の分子機構,
蛋白質核酸酵素, Vol.52, No.15, 1965-1972, 2007年12月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1524232505734459136

(CiNii: 1524232505734459136) Atsushi Ikeda, 山﨑哲男, Hiroshi Takeshima :
[Molecular basis of ryanodine receptor-mediated Ca2+ release],
蛋白質核酸酵素, Vol.52, No.15, 1965-1972, 2007年12月.

(キーワード): Animals / Calcium / Calcium Channels / Cell Membrane / Endoplasmic Reticulum / Ion Channels / Membrane Proteins / Ryanodine Receptor Calcium Release Channel
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18064887; ● Search Scopus @ Elsevier (PMID): 18064887

(PubMed: 18064887) 山﨑哲男 :
B細胞の分化・機能発現とBCAP,
臨床免疫, Vol.43, No.4, 483-486, 2005年4月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1521136280863139072

(CiNii: 1521136280863139072) 山﨑哲男 :
B細胞の分化・機能発現とBCAP,
臨床免疫, Vol.43, No.4, 483-486, 2005年4月. 山﨑哲男 :
B細胞の最終分化を決定するBCAPの核内転写因子c-Rel制御 (免疫細胞のシグナル伝達),
免疫 2006, Vol.2005, 165-170, 2005年.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1520854805196959488

(CiNii: 1520854805196959488) 山﨑哲男 :
B細胞の最終分化を決定するBCAPの核内転写因子c-Rel制御 (免疫細胞のシグナル伝達),
免疫, Vol.2005, 165-170, 2005年. 山﨑哲男 :
成熟B細胞の維持におけるB cell adaptor for PI3 kinase(BCAP)の役割,
臨床免疫, Vol.41, No.5, 574-577, 2004年5月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1520573330734682624

(CiNii: 1520573330734682624) 山﨑哲男 :
成熟B細胞の維持におけるB cell adaptor for PI3 kinase(BCAP)の役割,
臨床免疫, Vol.41, No.5, 574-577, 2004年5月. 山﨑哲男, 黒崎知博 :
B細胞シグナルにおけるアダプター分子の機能発現機構 (B細胞シグナル伝達),
医学のあゆみ, Vol.207, No.3, 174-178, 2003年10月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1521417755819914624

(CiNii: 1521417755819914624) 山﨑哲男 :
解説 B細胞の分化・機能発現とBCAP,
臨床免疫, Vol.39, No.2, 230-235, 2003年2月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1521417755421346432

(CiNii: 1521417755421346432) 山﨑哲男, 黒崎知博 :
新規アダプター分子BCAPによる免疫制御機構 (免疫研究の最前線--高次複雑系免疫システムの包括的理解をめざして) -- (リンパ球活性化・細胞死のシグナル制御),
蛋白質核酸酵素, Vol.47, No.16, 2242-2247, 2002年12月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1523669554538206592

(CiNii: 1523669554538206592) 山﨑哲男, Tomohiro Kurosaki :
[Immunoregulatory role for BCAP in B cell development and function],
蛋白質核酸酵素, Vol.47, No.16 Suppl, 2242-2247, 2002年12月.

(キーワード): 1-Phosphatidylinositol 3-Kinase / Adaptor Proteins, Signal Transducing / Animals / Antibody Formation / B-Lymphocytes / Carrier Proteins / Cell Differentiation / Mice / Phospholipase C gamma / Signal Transduction / Type C Phospholipases / src Homology Domains
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12518443; ● Search Scopus @ Elsevier (PMID): 12518443

(PubMed: 12518443) Tetsuo Yamazaki :
Interview about BCAP,
Modern Aspects of Immunobiol., Vol.2, 154, Mar. 2002.

(要約): BCAP was recently cloned as a binding molecule to phosphoinositide 3-kinase (PI3K). To investigate the role of BCAP, mutant mice deficient in BCAP were generated. While BCAP-deficient mice are viable, they have decreased numbers of mature B cells and B1 B cell deficiency. The mice produce lower titers of serum immunoglobulin (Ig)M and IgG3, and mount attenuated responses to T cell--independent type II antigen. Upon B cell receptor cross-linking, BCAP-deficient B cells exhibit reduced Ca(2+) mobilization and poor proliferative responses. These findings demonstrate that BCAP plays a pivotal immunoregulatory role in B cell development and humoral immune responses.
(キーワード): 1-Phosphatidylinositol 3-Kinase / Adaptor Proteins, Signal Transducing / Animals / Antibody Formation / B-Lymphocytes / Calcium / Carrier Proteins / Isoenzymes / Mice / Mice, Knockout / Phospholipase C gamma / Receptors, Antigen, B-Cell / Type C Phospholipases

山﨑哲男, 斉藤隆 :
T細胞抗原受容体を介するシグナル伝達 (特集免疫系における情報伝達とその異常),
最新医学, Vol.52, No.4, 759-767, 1997年4月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1523669555184799616

(CiNii: 1523669555184799616) 山﨑哲男, 斉藤隆 :
TCRシグナルによるT細胞選択の調節 (免疫生物学),
免疫(1996-97), No.1996, 101-111, 1996年8月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1521136280220425088

(CiNii: 1521136280220425088) 山﨑哲男, 斉藤隆 :
T細胞抗原受容体スーパーファミリー,
生体の科学, Vol.46, No.5, 556-560, 1995年10月.

(出版サイトへのリンク): ● Publication site (DOI): 10.11477/mf.2425901000
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.11477/mf.2425901000

(DOI: 10.11477/mf.2425901000)

講演・発表

Yuki Shiro and Tetsuo Yamazaki :
CTSD integrity in the endoplasmic reticulum is required for CLN6's anti-aggregate activity,
The 20th annual WORLDSymposium 2024, San Diego, Feb. 2024. Yuki Shiro and Tetsuo Yamazaki :
Novel insight into the compound heterozygosity-driven CLN6 disease pathomechanism,
The 18th annual WORLDSymposium 2022, California, Feb. 2022. Yuki Shiro and Tetsuo Yamazaki :
Contribution of functional interference between CLN6 mutants to the pathogenesis of the neuronal ceroid lipofuscinoses,
The 17th International Congress on Neuronal Ceroid Lipofuscinosis, St Louis, Oct. 2021. Yuki Shiro and Tetsuo Yamazaki :
Implications of graded reductions in CLN6's anti-aggregate activity as a pathomechanism of the neuronal ceroid lipofuscinoses,
The 45th FEBS Congres, Ljubljana, Jul. 2021. Yuki Shiro and Tetsuo Yamazaki :
Differential impairment of CLN6s anti-aggregate activity as a pathogenic mechanism of CLN6 disease,
17th annual WORLDSymposium 2021, Minnesota, Feb. 2021. Arisa Yamashita and Tetsuo Yamazaki :
ER-driven anti-aggregate activity toward pathogenic alphaB-crystallin mutants,
The 43rd FEBS Congress, Praha, Jul. 2018. Arisa Yamashita, Takamitsu Nakatsuru, Hiroki Saito, Yuri Hiraki and Tetsuo Yamazaki :
ER Manipulation: A promising therapeutic intervention for protein aggregation diseases,
The 3rd International Symposium on Regenerative Rehabilitation in Kyoto, Kyoto, Feb. 2017. Tetsuo Yamazaki :
ER as a potential therapeutic target for protein aggregation disease,
The Fifth Bizan Immunology Symposium at The University of Tokushima, Tokushima, Mar. 2016. Tetsuo Yamazaki :
Manipulation of the ER: a novel strategy against protein desposition disease.,
The Fourth Bizan Immunology Symposium at The University of Tokushima, Tokushima, Jan. 2015. 塚本陽花, 城裕己, 山﨑哲男 :
Cathepsin D前駆体は小胞体膜分子CLN6と協働して蛋白質凝集を抑制する,
第22回四国免疫フォーラム, 2024年6月. 片山将一, 塚本陽花, 城裕己, 山﨑哲男 :
P19細胞の神経細胞分化時におけるcyclin-dependent kinase-like 5の機能とリン酸化状態,
日本薬学会第144年会(神奈川), 2024年3月. 城裕己, 山﨑哲男 :
プロカテプシンDは小胞体で機能していた,
超異分野学会香川フォーラム2023, 2023年12月. 渡邊佳奈, 城裕己, 片山将一, 山﨑哲男 :
CLN6 Pro299Leu変異体における分子内相互作用がタンパク質安定性を左右する,
第62回日本薬学会中国四国支部学術大会(高知), 2023年10月. 城裕己, 山﨑哲男 :
CLN10は変異により細胞内局在が変わる,
超異分野学会大阪大会2023, 2023年8月. 城裕己, 山﨑哲男 :
Cathepsin Dは小胞体内腔でCLN6の凝集抑制能を支える,
第21回四国免疫フォーラム, 2023年6月. 城裕己, 片山将一, 山﨑哲男 :
CLN10 A58V変異体は小胞体膜微小環境に備わる凝集抑止機能を阻害する,
日本薬学会第143年会(北海道), 2023年3月. 渡邊佳奈, 城裕己, 片山将一, 山﨑哲男 :
CLN6のC末端領域変異における凝集抑止機能とタンパク質安定性に基づいたCLN6病の発症要因検討,
日本薬学会第143年会(北海道), 2023年3月. 片山将一, 城裕己, 山﨑哲男 :
Cyclin-dependent kinase-like 5のin vitro神経細胞分化における役割,
日本薬学会第143年会(北海道), 2023年3月. 城裕己, 山﨑哲男 :
CLN10変異体のもつ凝集抑止機能と疾患の関連性,
超異分野学会大阪大会2022, 2022年8月. 城裕己, 山﨑哲男 :
Cathepsin Dによる小胞体膜微小環境の制御機構解明,
第20回四国免疫フォーラム, 2022年6月. 片山将一, 城祐己, 山﨑哲男 :
Cyclin-dependent kinase-like 5の酵素活性をin celluloにおいて検出する手法の開発,
日本薬学会第142年会(愛知), 2022年3月. 城裕己, 山﨑哲男 :
小胞体膜微小環境におけるCLN6-CLN10複合体は凝集抑止機能を制御する,
日本薬学会第142年会, 2022年3月. 城裕己, 山﨑哲男 :
小胞体駆動の凝集抑止が神経変性疾患を防ぐ,
超異分野学会東京大会2022, 2022年3月. 城裕己, 山﨑哲男 :
小胞体膜近傍タンパク質複合体の障害による凝集体蓄積疾患の発症メカニズム,
第112回蔵本免疫懇話会, 2022年1月. 城裕己, 山﨑哲男 :
稀少疾患CLN6病の発病予測システムの開発に向けて,
超異分野学会香川フォーラム2021, 2021年12月. 片山将一, 城裕己, 山﨑哲男 :
人工基質を用いたcyclin-dependent kinase-like 5 の基質リン酸化活性を検出する手法の開発,
第44回日本分子生物学会, 2021年12月. 城裕己, 山﨑哲男 :
CLN6のC末端領域変異体が凝集抑止機能を喪失するメカニズムの解析,
第44回日本分子生物学会, 2021年12月. 城裕己, 山﨑哲男 :
小胞体を中心とするタンパク質恒常性を支える分子メカニズムの解明,
第4回 kenQ-Pitch Osaka, 2021年11月. 片山将一, 城裕己, 山﨑哲男 :
Phos-tag SDS-PAGEを利用したcyclin-dependent kinase-like 5の基質リン酸化検出法の開発,
第60回日本薬学会中国四国支部学術大会, 2021年10月. 渡邉佳奈, 城裕己, 山﨑哲男 :
複合ヘテロ接合型CLN6病における凝集抑止活性を消失させる新たなメカニズムの解明,
第60回日本薬学会中国四国支部学術大会, 2021年10月. 城裕己, 山﨑哲男 :
CLN6 P299L変異を有する複合ヘテロ接合型CLN6病の臨床症状を検討する,
日本人類遺伝学会第66回大会, 2021年10月. 城裕己, 山﨑哲男 :
CLN6のフレームシフト変異体(S132fs)はミスセンス変異体(P299L)の機能を喪失させる,
日本遺伝学会第93回大会, 2021年9月. 城裕己, 山﨑哲男 :
凝集体難病予防に向けた小胞体膜タンパク質品質管理機構の解明,
第20回次世代を担う若手ファーマ・バイオフォーラム2021, 2021年8月. 城裕己, 山﨑哲男 :
小胞体膜を取り巻く相互作用分子の可能性,
第2回 kenQ-Pitch Osaka, 2021年8月. 城裕己, 山﨑哲男 :
凝集抑止活性を指標とした複合ヘテロ接合型CLN6病の発症メカニズム検討,
第61回日本先天異常学術集会, 2021年8月. 城裕己, 山﨑哲男 :
小胞体膜に備わる凝集抑止機能の制御メカニズム解明,
第1回 kenQ-Pitch Osaka, 2021年6月. 城裕己, 山﨑哲男 :
複合ヘテロ接合型CLN6病における凝集抑止機能の制御メカニズム解明,
第19回四国免疫フォーラム, 2021年6月. 城裕己, 山﨑哲男 :
稀少疾患CLN6病の発症メカニズム解明,
超異分野学会大阪大会2021, 2021年4月. 城裕己, 山﨑哲男 :
複合ヘテロ接合型CLN6病の原因として見出した抗凝集体活性の喪失,
日本薬学会第141年会, 2021年3月. 片山将一, 城裕己, 山﨑哲男 :
Cyclin-dependent kinase-like 5の酵素活性をin celluloにおいて検出する手法の開発,
日本薬学会第142年会, 2021年3月. 城裕己, 山﨑哲男 :
小胞体膜を使って凝集を防ぐ,
第10回超異分野学会, 2021年3月. 城裕己, 山﨑哲男 :
CLN6変異による抗凝集体活性の喪失とCLN6病発症の関係,
第59回日本薬学会中国四国支部学術大会, 2020年12月. 城裕己, 山下ありさ, 平木友理, 湯尻貴俊, 山﨑哲男 :
小胞体膜微小環境に備わる抗凝集体活性の障害がCLN6病を引き起こす,
稀少疾患カンファランス, 2019年8月. 山﨑哲男 :
小胞体膜微小環境病としての神経セロイドリポフスチン症,
立命館大学稀少疾患プロジェクトオープンセミナー, 2019年6月. 山下ありさ, 平木友理, 山﨑哲男 :
小胞体マニピュレーションの汎用性とその分子基盤,
第17回四国免疫フォーラム, 2018年6月. 山﨑哲男 :
タンパク質凝集体難病の克服に向けた小胞体操作法の開発,
立命館大学稀少疾患プロジェクトオープンセミナー, 2017年6月. 山下ありさ, 平木友理, 山﨑哲男 :
小胞体マニピュレーションがもたらす抗凝集体活性の分子基盤,
第16回四国免疫フォーラム, 2017年6月. 山﨑哲男 :
凝集体難病の克服に向けた小胞体操縦法,
福井大学医学系研究科第567回学内セミナー (大学院セミナー), 2017年1月. 山下ありさ, 山﨑哲男 :
タンパク質凝集体難病の克服に向けた小胞体操作の分子基盤,
第15回四国免疫フォーラム, 2016年6月. 山下ありさ, 山﨑哲男 :
小胞体を標的とした凝集体難病治療法開発,
第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2015年10月. 山下ありさ, 山﨑哲男 :
小胞体マニピュレーションに基づく凝集難病治療法の創出,
第14回四国免疫フォーラム, 2015年6月. 山本伸一郎, 山﨑哲男 :
タンパク質品質管理機構における calumin の役割,
第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月. 中西智子, 石澤啓介, 阿部真治, 中瀬真理, 柴田洋文, 佐藤智恵美, 新垣尚捷, 佐藤陽一, 山﨑尚志, 笠原二郎, 東満美, 山﨑哲男, 山内あい子, 滝口祥令, 土屋浩一郎 :
アドバンスト演習を通した問題解決能力向上のための症例解析手法の検討-プロダクトからの分析,
日本薬学会第134年会, 2014年3月. 中西智子, 石澤啓介, 阿部真治, 中瀬真理, 柴田洋文, 佐藤智恵美, 新垣尚捷, 佐藤陽一, 山﨑尚志, 笠原二郎, 東満美, 山﨑哲男, 山内あい子, 滝口祥令, 土屋浩一郎 :
アドバンスト演習を通した問題解決能力向上のための症例解析手法の検討,
第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2013年10月. 吉良太孝, 山下ありさ, 山中直哉, 古川和寛, 山﨑哲男, 石田竜弘, 際田弘志, 南川典昭 :
ケミカルツールを用いたsiRNA-タンパク質間の相互作用様式解明,
第133年会日本薬学会, 2013年3月. 山下ありさ, 山﨑哲男 :
小胞体タンパク質EPIGは紫外線照射による細胞死を抑制する,
第51回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2012年11月. 駒田致和, 新垣尚捷, 山﨑哲男 :
ミトコンドリア由来のROSシグナルは骨芽細胞の分化を誘導する,
第51回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2012年11月. 本藤栄里, 桝井俊輔, 山﨑哲男 :
小胞体タンパク質EPIGの紫外線応答における役割,
第50回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2011年11月. 山﨑哲男 :
DNA損傷応答を規定する小胞体のシグナル特性,
平成23年度第3回革新的特色研究シンポジウム「分子イメージング手法を導入した免疫疾患克服の革新的研究」, 2011年11月. 山﨑哲男 :
遺伝情報システムと免疫システムのクロストーク,
平成22年度第3回革新的特色研究シンポジウム「分子イメージング手法を導入した免疫疾患克服の革新的研究」, 2010年11月. 石澤啓介, 中西智子, 柴田洋文, 阿部真治, 杉村真由美, 奥村千恵子, 吉村好之, 佐藤陽一, 新垣尚捷, 川添和義, 東満美, 土屋浩一郎, 山内あい子, 山﨑哲男, 水口和生 :
徳島大学における薬学部・薬剤部連携による病院実務実習の実践,
第20回日本医療薬学会年会, 2010年11月. 渡邉美穂, 柴田洋文, 上松卓, 伏谷秀治, 阿部真治, 川添和義, 山﨑哲男, 水口和生 :
病院施設のATP拭き取り検査と細菌汚染状況調査,
第49回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2010年11月. 山﨑哲男 :
小胞体のシグナル特性から免疫へ,
免疫シグナルシンポジウム, 2010年10月. 桝井俊輔, 山﨑哲男 :
小胞体タンパク質MG23によるDNA損傷誘導性細胞死の促進,
第117回日本薬理学会近畿部会, 2010年7月. 石澤啓介, 川添和義, 東満美, 土屋浩一郎, 山内あい子, 山﨑哲男, 水口和生, 中西智子, 柴田洋文, 阿部真治, 杉村真由美, 奥村千恵子, 吉村好之, 佐藤陽一, 新垣尚捷 :
P1-571 徳島大学における薬学部・薬剤部連携による病院実務実習の実践(一般演題ポスター発表,薬学教育(実務実習),臨床から学び臨床へと還元する医療薬学),
日本医療薬学会年会講演要旨集, Vol.20, No.0, 382, 2010年.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390845713041900800

(CiNii: 1390845713041900800)

研究会・報告書: 瀬戸田紋李, 塚本陽花, 城裕己, 渡邊佳奈, 片山将一, 山﨑哲男 :
AlphaFold2を用いてCLN6の分子内相互作用を予測する,
徳島大学大学院医歯薬学研究部 2023年度感染免疫クラスター・ミニリトリート(徳島), 2024年2月. 塚本陽花, 城裕己, 山﨑哲男 :
AlphaFold2を用いたCLN6の分子内相互作用解析,
超異分野学会香川フォーラム2023, 2023年12月. 塚本陽花, 城裕己, 片山将一, 山﨑哲男 :
AlphaFold2を用いた疾患発症メカニズムの検討,
徳島医理工連携会議(徳島), 2023年11月. 植野美彦, 関陽介, 衣川仁, 森岡久尚, 髙橋章, 森健治, 石丸直澄, 尾崎和美, 山﨑哲男, 高田篤, 宇都義浩, 齊藤隆仁, 上岡麻衣子 :
令和4年度徳島大学高等教育研究センターアドミッション部門報告書,
令和4年度徳島大学高等教育研究センターアドミッション部門報告書, 2023年3月.

特許: 研究者総覧に該当データはありませんでした。
作品: 研究者総覧に該当データはありませんでした。
補助金・競争的資金: 重度精神発達障害の原因遺伝子CDKL5の神経細胞分化を制御する分子メカニズムの解明 (研究課題/領域番号: 23K05148 )
小胞体膜分子CLN6の凝集抑止能を制御する分子メカニズムの解明 (研究課題/領域番号: 22K06146 )
小胞体マニピュレーションを基盤とする凝集体難病の治療戦略 (研究課題/領域番号: 18K07045 )
小胞体を新規標的に据えたタンパク質凝集体難病治療法の創出 (研究課題/領域番号: 15K08404 )
細胞膜ＡＴＰ合成酵素を介した新規脂質代謝調節機構の解明と新規抗肥満薬の開発 (研究課題/領域番号: 24590081 )
小胞体分子 MG23 による DNA損傷応答と光免疫応答のクロストーク (研究課題/領域番号: 22590359 )
新規小胞体分子caluminによる細胞内小器官発シグナルの制御機構の解明 (研究課題/領域番号: 19590267 )
BCAP結合分子BB1による発がん制御機構の解明 (研究課題/領域番号: 17590263 )
アダプター分子BCAPによる発がん抑制機構の機序解明 (研究課題/領域番号: 16021253 )
アダプター分子BCAPの機能発現機序の解明 (研究課題/領域番号: 15790255 )
免疫システムにおけるシグナルの量的・質的制御 (研究課題/領域番号: 13854013 )
B細胞アダプター分子BLNKに結合する新規蛋白質の機能解析 (研究課題/領域番号: 13770165 )
モデルB細胞を用いた細胞増殖・細胞死制御におけるPI3K活性化の分子機構 (研究課題/領域番号: 13214105 )
マクロファージ分化・活性化における新規アダプター分子BCAPの役割 (研究課題/領域番号: 13016217 )
研究者番号（90330208）による検索

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2024年11月14日更新

専門分野・研究分野: 生化学 (Biochemistry)
所属学会・所属協会: 日本薬学会
四国免疫フォーラム
社団法人日本リハビリテーション医学会
委員歴・役員歴: 四国免疫フォーラム (世話人 [2010年4月〜2025年3月])
受賞: 2018年8月, 平成29年度特別研究員等審査会専門委員表彰 (独立行政法人日本学術振興会)
活動: 独立行政法人日本学術振興会 (卓越研究員候補者選考委員会書面審査員・書面評価員 [2017年8月〜2018年7月])
独立行政法人日本学術振興会 (特別研究員等審査会専門委員 [2016年8月〜2018年7月])
実務実習運営委員会 (2010年4月〜2019年3月)
スキルスラボ運営委員会委員 (2010年10月〜2021年3月)
薬剤業務協議会 (2011年4月〜2013年3月)
学生委員会委員 (2011年4月〜2015年3月)
FD委員会委員 (2011年4月〜2019年3月)
廃棄物等処理委員会廃棄物等取扱主任者 (2011年4月〜2021年3月)
徳島大学病原体等安全管理委員会委員 (2011年11月〜2019年3月)
教務委員会委員 (2016年4月〜2017年3月)
将来構想委員会委員 (2016年4月〜2017年3月)
大学院医歯薬学研究部倫理委員会委員 (2016年4月〜2017年3月)
徳島大学薬学部FD委員会委員長 (2016年4月〜2019年3月)
徳島大学サマープログラム等実施委員会委員 (2016年4月〜2019年3月)
防災環境委員会委員長 (2016年4月〜2021年3月)
環境保全活動責任者 (2016年4月〜2021年3月)
薬学部実務実習運営委員会委員 (2016年4月〜2021年3月)
薬学部廃棄物等処理委員会廃棄物等取扱主任者 (2016年4月〜2021年3月)
環境防災研究センター運営委員会運営委員 (2016年4月〜2021年3月)
徳島大学薬学部FD委員会副委員長 (2020年4月〜2021年3月)

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Ｊグローバル

Jグローバル最終確認日: 2024/11/9 01:04
氏名（漢字）: 山﨑哲男
氏名（フリガナ）: ヤマザキテツオ
氏名（英字）: Yamazaki Tetsuo
所属機関: 徳島大学教授

リサーチマップ

researchmap最終確認日: 2024/11/10 02:34
氏名（漢字）: 山﨑哲男
氏名（フリガナ）: ヤマザキテツオ
氏名（英字）: Yamazaki Tetsuo
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登録日時: 2020/10/9 16:15
更新日時: 2024/11/9 06:28
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所属: 徳島大学
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ＫＡＫＥＮで最新データを確認する

2024年11月9日更新

研究者番号: 90330208

所属（現在）: 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学域), 教授

所属（過去の研究課題 情報に基づく）*注記: 2022/4/1 – 2023/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学域), 教授
2018/4/1 – 2020/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学域), 教授
2016/4/1 – 2017/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学系), 教授
2015/4/1 : 徳島大学, 大学院医歯薬学研究部, 教授
2014/4/1 : 徳島大学, 大学院ヘルスバイオサイエンス研究部, 教授
2012/4/1 – 2014/4/1 : 徳島大学, ヘルスバイオサイエンス研究部, 教授
2010/4/1 – 2012/4/1 : 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授
2007/4/1 – 2008/4/1 : 京都大学, 薬学研究科, 准教授
2006/4/1 : 東北大学, 大学院医学系研究科, COEフェロー
2004/4/1 – 2005/4/1 : 東北大学, 大学院・医学系研究科, COEフェロー
2004/4/1 : 東北大学, 大学院・医学研究科, COEフェロー
2001/4/1 – 2003/4/1 : 関西医科大学, 医学部, 助手

審査区分/研究分野

研究代表者

医学 / 病理 / 免疫学
生物系 / 医歯薬学 / 基礎医学 / 免疫学
生物系 / 医歯薬学 / 基礎医学 / 医化学一般
生物系 / 医歯薬学 / 基礎医学 / 実験病理学
生物系 / 医歯薬学 / 基礎医学 / 病態医化学
生物系
小区分49030:実験病理学関連
小区分43030:機能生物化学関連

研究代表者以外

生物系 / 医歯薬学 / 薬学 / 生物系薬学
医学 / 病理 / 免疫学
生物系
小区分38060:応用分子細胞生物学関連

キーワード

研究代表者

BCR / BLNK / Ruk / CD2-AP / PI3K / DT40 / BCAP / c-Rel / アダプター分子 / 転写因子 / 抗体反応 / アダプター分化 / 発がん / NF-κB / カルシウム / 小胞体 / 細胞内小器官 / シグナル / 細胞死 / シグナル伝達 / 紫外線 / DNA損傷 / ゲノム / 免疫応答 / 癌 / 遺伝子 / 発現制御 / 細胞・組織 / cancer / signal transduction / gene / regulation of expression / cell・tissue / CLN6 / 凝集体 / クリスタリン / リソゾーム病 / 難病 / NCL / ER / 神経セロイドリポフスチン症 / 神経性セロイドリポフスチン症 / Kufs病 / Batten病 / リポフスチン症

研究代表者以外

BCAP / マクロファージ / PI3K / アダプター分子 / シグナル伝達 / B細胞分化 / ノックアウトマウス / p85サブユニット / Akt活性化 / JNK活性化 / DT40細胞 / Ｆ１Ｆｏ-ＡＴＰ合成酵素 / 脂肪細胞 / 細胞内中性脂肪 / 抗肥満薬 / ＡＴＰ / ＡＴＰ受容体 / ミトコンドリア / 国際情報交換 / BCR / エフェクター分子 / Bリンパ球分化 / 免疫応答 / PI3キナーゼ / B細胞活性化 / BANK / CD40 / B細胞活性 / アダプター分化 / 転写因子 / c-Rel / BLNK / PLC-γ2 / 抗原反応 / adaptor molecules / effector molecules / signal transduction / B lymphocyte development / immune response / CDKL5 / プロテインキナーゼ / 細胞内シグナル伝達 / 神経細胞分化 / ゼブラフィッシュ

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山﨑 哲男

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山﨑哲男