2021/10/20 更新

写真a

サトウ トキハル
佐藤 時春
SATO Tokiharu
所属
脳研究所 特任助教
職名
特任助教
外部リンク

学位

  • 博士(医学) ( 2008年12月   金沢大学 )

研究キーワード

  • 神経変性

  • 神経再生

  • 神経科学

研究分野

  • ライフサイエンス / 神経形態学

経歴(researchmap)

  • 新潟大学   脳研究所   特任助教

    2019年2月 - 現在

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  • テキサス大学ヒューストン校   医学部   博士研究員

    2015年10月 - 2019年1月

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  • 金沢大学   がん進展制御研究所   助教

    2012年4月 - 2015年9月

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  • 金沢大学   がん研究所   助教

    2009年1月 - 2012年3月

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経歴

  • 新潟大学   脳研究所 生命科学リソース研究センター   特任助教

    2019年2月 - 現在

学歴

  • 金沢大学   医学系研究科

    - 2008年12月

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    国名: 日本国

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  • 金沢大学

    - 2008年

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所属学協会

 

論文

  • Direct Comparison of Odor Responses of Homologous Glomeruli in the Medial and Lateral Maps of the Mouse Olfactory Bulb 査読

    Tokiharu Sato, Ryota Homma, Shin Nagayama

    eNeuro   7 ( 2 )   0449-19   2020年1月

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    担当区分:筆頭著者   掲載種別:研究論文(学術雑誌)  

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  • Narrowly confined and glomerulus-specific onset latencies of odor-evoked calcium transients in the juxtaglomerular cells of the mouse main olfactory bulb 査読

    Homma R, Lv X, Sato T, Imamura F, Zeng S, Nagayama S

    eNeuro   10   1523   2019年2月

  • The osteopontin-CD44 axis in hepatic cancer stem cells regulates IFN signaling and HCV replication. 査読 国際誌

    Takayoshi Shirasaki, Masao Honda, Taro Yamashita, Kouki Nio, Tetsuro Shimakami, Ryougo Shimizu, Saki Nakasyo, Kazuhisa Murai, Natsumi Shirasaki, Hikari Okada, Yoshio Sakai, Tokiharu Sato, Tetsuro Suzuki, Katsuji Yoshioka, Shuichi Kaneko

    Scientific reports   8 ( 1 )   13143 - 13143   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Osteopontin (OPN) is involved in cell proliferation, migration, inflammation, and tumor progression in various tissues. OPN induces stemness by interacting with CD44, but the functional relevance of OPN-mediated interferon (IFN) signaling and hepatitis C virus (HCV) replication in stem cell populations remains unclear. In this study, we investigated the effect of OPN on HCV replication and IFN signaling in cancer stem cells (CSCs) positive for epithelial cell adhesion molecule (EpCAM) and CD44. We show that the EpCAM+/CD44+ CSCs show marked HCV replication when compared to EpCAM-/CD44- cells. In addition, OPN significantly enhances this HCV replication in EpCAM+/CD44+ CSCs and markedly suppresses IFN-stimulated gene expression. The GSK-3β inhibitor BIO increases the EpCAM+/CD44+ CSC population and OPN expression and impairs IFN signaling via STAT1 degradation. Taken together, our data suggest that OPN enhances HCV replication in the EpCAM+/CD44+ CSCs, while it also negatively regulates the IFN signaling pathway via inhibition of STAT1 phosphorylation and degradation. Therefore, OPN may represent a novel therapeutic target for treating HCV-related hepatocellular carcinoma.

    DOI: 10.1038/s41598-018-31421-6

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  • Critical role of JSAP1 and JLP in axonal transport in the cerebellar Purkinje cells of mice 査読

    Tokiharu Sato, Momoe Ishikawa, Toru Yoshihara, Ryota Nakazato, Haruhiro Higashida, Masahide Asano, Katsuji Yoshioka

    FEBS LETTERS   589 ( 19 )   2805 - 2811   2015年9月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    JNK/stress-activated protein kinase-associated protein 1 (JSAP1) and JNK-associated leucine zipper protein (JLP) are structurally related scaffolding proteins that are highly expressed in the brain. Here, we found that JSAP1 and JLP play functionally redundant and essential roles in mouse cerebellar Purldnje cell (PC) survival. Mice containing PCs with deletions in both JSAP1 and JLP exhibited PC axonal dystrophy, followed by gradual, progressive neuronal loss. Kinesin-1 cargoes accumulated selectively in the swollen axons of Jsap1/Jlp-deficient PCs. In addition, autophagy inactivation in these mice markedly accelerated PC degeneration. These findings suggest that JSAP1 and JLP play critical roles in kinesin-1-dependent axonal transport, which prevents brain neuronal degeneration. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.febslet.2015.08.024

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  • JSAP1/JIP3 and JLP regulate kinesin-1-dependent axonal transport to prevent neuronal degeneration 査読

    T. Sato, M. Ishikawa, M. Mochizuki, M. Ohta, M. Ohkura, J. Nakai, N. Takamatsu, K. Yoshioka

    CELL DEATH AND DIFFERENTIATION   22 ( 8 )   1260 - 1274   2015年8月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Axonal transport is critical for neuronal development and function, and defective axonal transport has been implicated in neurodegenerative diseases. However, how axonal transport is regulated, or how defective transport leads to neuronal degeneration, remains unclear. Here, we report that c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as JNK-interacting protein 3 (JIP3)) and JNK-associated leucine zipper protein (JLP) are essential for postnatal brain development. Mice with a double-knockout (dKO) in Jsap1 and Jlp in the dorsal telencephalon developed progressive neuron loss. Using a primary neuron culture system with induced disruption of targeted genes, combined with gene rescue experiments, we show that JSAP1 and JLP regulate kinesin-1-dependent axonal transport with functional redundancy. We also show that the binding of JSAP1 and JLP to kinesin-1 heavy chain is crucial for interactions between kinesin-1 and microtubules. Furthermore, we describe a molecular mechanism by which defective kinesin-1-dependent axonal transport in Jsap1: Jlp dKO neurons causes axonal degeneration and subsequent neuronal death. JNK hyperactivation because of increased intra-axonal Ca2+ in the Jsap1: Jlp dKO neurons was found to mediate both the axonal degeneration and neuronal death, in cooperation with the Ca2+-dependent protease calpain. Our results indicate that axonal JNK may relocate to the nucleus in a dynein-dependent manner, where it activates the transcription factor c-Jun, resulting in neuronal death. Taken together, our data establish JSAP1 and JLP as positive regulators of kinesin-1-dependent axonal transport, which prevents neuronal degeneration.

    DOI: 10.1038/cdd.2014.207

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  • JSAP1 and JLP are required for ARF6 localization to the midbody in cytokinesis 査読

    Baljinnyam Tuvshintugs, Tokiharu Sato, Radnaa Enkhtuya, Katsumi Yamashita, Katsuji Yoshioka

    GENES TO CELLS   19 ( 9 )   692 - 703   2014年9月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    The ADP-ribosylation factor 6 (ARF6) GTPase is important in cytokinesis and localizes to the midbody. However, the mechanism and regulation of ARF6's recruitment to the midbody are largely unknown. Here, we investigated the functions of two binding partners of active ARF6, c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1) and JNK-associated leucine zipper protein (JLP), by gene knockout and rescue experiments in mouse embryonic fibroblasts. Depleting both JSAP1 and JLP impaired ARF6's localization to the midbody and delayed cytokinesis. These defects were almost completely rescued by wildtype JSAP1 or JLP, but not by JSAP1 or JLP mutants that were unable to interact with active ARF6 or with the kinesin heavy chain (KHC) of kinesin-1. In transfected cells, a constitutively active form of ARF6 associated with KHC only when co-expressed with wild-type JSAP1 or JLP and not with a JSAP1 or JLP mutant. These findings suggest that JSAP1 and JLP, which might be paralogous to each other, are critical and functionally redundant in cytokinesis and control ARF6 localization to the midbody by forming a tripartite complex of JSAP1/JLP, active ARF6, and kinesin-1.

    DOI: 10.1111/gtc.12170

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  • The scaffold protein JLP plays a key role in regulating ultraviolet B-induced apoptosis in mice 査読

    Radnaa Enkhtuya, Tokiharu Sato, Mitsuo Wakasugi, Baljinnyam Tuvshintugs, Hirofumi Miyata, Takeshi Sakurai, Tsukasa Matsunaga, Katsuji Yoshioka

    GENES TO CELLS   19 ( 4 )   350 - 358   2014年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    The ultraviolet B (UVB) component of sunlight can cause severe damage to skin cells and even induce skin cancer. Growing evidence indicates that the UVB-induced signaling network is complex and involves diverse cellular processes. In this study, we investigated the role of c-Jun NH2-terminal kinase-associated leucine zipper protein (JLP), a scaffold protein for mitogen-activated protein kinase (MAPK) signaling cascades, in UVB-induced apoptosis. We found that UVB-induced skin epidermal apoptosis was prevented in Jlp knockout (KO) as well as in keratinocyte-specific Jlp KO mice. Analysis of the repair of UVB-induced DNA damage over time showed no evidence for the involvement of JLP in this process. In contrast, UVB-stimulated p38 MAPK activation in the skin was impaired in both Jlp KO and keratinocyte-specific Jlp KO mice. Moreover, topical treatment of UVB-irradiated mouse skin with a p38 inhibitor significantly suppressed the epidermal apoptosis in wild-type mice, but not in Jlp KO mice. Our findings suggest that JLP in skin basal keratinocytes plays an important role in UVB-induced apoptosis by modulating p38 MAPK signaling pathways. This is the first study to show a critical role for JLP in an in vivo response to environmental stimulation.

    DOI: 10.1111/gtc.12135

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  • Human microRNA-1245 down-regulates the NKG2D receptor in natural killer cells and impairs NKG2D-mediated functions 査読

    J. Luis Espinoza, Akiyoshi Takami, Katsuji Yoshioka, Katsuya Nakata, Tokiharu Sato, Yoshihito Kasahara, Shinji Nakao

    HAEMATOLOGICA-THE HEMATOLOGY JOURNAL   97 ( 9 )   1295 - 1303   2012年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FERRATA STORTI FOUNDATION  

    Background
    NKG2D is an activating receptor expressed by natural killer and T cells, which have crucial functions in tumor and microbial immunosurveillance. Several cytokines have been identified as modulators of NKG2D receptor expression. However, little is known about NKG2D gene regulation. In this study, we found that microRNA 1245 attenuated the expression of NKG2D in natural killer cells.
    Design and Methods
    We investigated the potential interactions between the 3'-untranslated region of the NKG2D gene and microRNA as well as their functional roles in the regulation of NKG2D expression and cytotoxicity in natural killer cells.
    Results
    Transforming growth factor-beta 1, a major negative regulator of NKG2D expression, post-transcriptionally up-regulated mature microRNA-1245 expression, thus down-regulating NKG2D expression and impairing NKG2D-mediated immune responses in natural killer cells. Conversely, microRNA-1245 down-regulation significantly increased the expression of NKG2D expression in natural killer cells, resulting in more efficient NKG2D-mediated cytotoxicity.
    Conclusions
    These results reveal a novel NKG2D regulatory pathway mediated by microRNA-1245, which may represent one of the mechanisms used by transforming growth factor-beta 1 to attenuate NKG2D expression in natural killer cells.

    DOI: 10.3324/haematol.2011.058529

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  • Role of plasma membrane localization of the scaffold protein JSAP1 during differentiation of cerebellar granule cell precursors 査読

    Tokiharu Sato, Anir Enkhbat, Katsuji Yoshioka

    GENES TO CELLS   16 ( 1 )   58 - 68   2011年1月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    We previously reported that the scaffold protein c-Jun NH(2)-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1) functions in cerebellar granule cell precursors (GCPs) to promote their cell-cycle exit and differentiation. In this study, we used immunocytochemistry to examine the subcellular distribution of JSAP1 in proliferating cultured GCPs. We found that when stimulated with fibroblast growth factor-2 (FGF-2), a factor that promotes GCP differentiation through JNK and extracellular signal-regulated kinase (ERK) signaling, JSAP1 translocated to the plasma membrane and colocalized with activated JNK and ERK. In transfected cells expressing a constitutively activated FGF receptor (FGFR), JSAP1 and the activated FGFR colocalized at the plasma membrane with not only activated but also unphosphorylated and inactive JNK and ERK. These colocalizations did not occur when a mutant JSAP1 lacking the JNK-binding domain was substituted for wild-type JSAP1. Biochemical analyses of transfected cells showed that activated FGFR increased JSAP1's affinity for JNK and ERK and that JSAP1 enhanced FGFR-induced JNK and ERK activation. Collectively, these results suggest that when stimulated by FGFR, JSAP1 translocates to the plasma membrane, where it recruits JNK and ERK and facilitates their activation, leading to the differentiation of cerebellar GCPs.

    DOI: 10.1111/j.1365-2443.2010.01465.x

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  • Ablation of the scaffold protein JLP causes reduced fertility in male mice 査読

    Asuka Iwanaga, Guangmin Wang, Davaakhuu Gantulga, Tokiharu Sato, Tuvshintugs Baljinnyam, Keiko Shimizu, Ken Takumi, Motoharu Hayashi, Takuya Akashi, Hideki Fuse, Kazushi Sugihara, Masahide Asano, Katsuji Yoshioka

    Transgenic Research   17 ( 6 )   1045 - 1058   2008年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The specific and efficient activation of mitogen-activated protein kinase (MAPK) signaling modules is mediated, at least in part, by scaffold proteins. c-Jun NH2-terminal kinase (JNK)-associated leucine zipper protein (JLP) was identified as a scaffold protein for JNK and p38 MAPK signaling modules. JLP is expressed nearly ubiquitously and is involved in intracellular signaling pathways, such as the Gα13 and Cdo-mediated pathway, in vitro. To date, however, JLP expression has not been analyzed in detail, nor are its physiological functions well understood. Here we investigated the expression of JLP in the mouse testis during development. Of the tissues examined, JLP was strongest in the testis, with the most intense staining in the elongated spermatids. Since the anti-JLP antibody used in this study can recognize both JLP and sperm-associated antigen 9 (SPAG9), a splice variant of JLP that has been studied extensively in primates, we also examined its expression in macaque testis samples. Our results indicated that in mouse and primate testis, the isoform expressed at the highest level was JLP, not SPAG9. We also investigated the function of JLP by disrupting the Jlp gene in mice, and found that the male homozygotes were subfertile. Taken together, these observations may suggest that JLP plays an important role in testis during development, especially in the production of functionally normal spermatozoa. © 2008 Springer Science+Business Media B.V.

    DOI: 10.1007/s11248-008-9191-6

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  • Ablation of the scaffold protein JLP causes reduced fertility in male mice. 査読

    Iwanaga A, Wang G, Gantulga D, Sato T, Baljinnyam T, Shimizu K, Takumi K, Hayasi M, Akashi T, Fuse H, Sugihara K, Asano M, Yoshioka K

    Transgenic Research   17 ( 6 )   1045 - 1058   2008年12月

  • The scaffold protein JSAP1 regulates proliferation and differentiation of cerebellar granule cell precursors by modulating JNK signaling 査読

    Tokiharu Sato, Takashi Torashima, Kazushi Sugihara, Hirokazu Hirai, Masahide Asano, Katsuji Yoshioka

    MOLECULAR AND CELLULAR NEUROSCIENCE   39 ( 4 )   569 - 578   2008年11月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Cerebellar granule cell precursors (GCPs) proliferate in the Outer part of the external granular layer (EGL). They begin their differentiation by exiting the cell cycle and migrating into the inner part of the EGL. Here we report that JSAP1, a scaffold protein for JNK signaling pathways, is expressed predominantly in the post-mitotic GCPs of the inner EGL. JSAP1 knockdown or treatment with a JNK inhibitor enhances the proliferation Of Cultured GCPs, but the overexpression of wild-type JSAP1 leads to increased proportions of p27(Kip1)- and NeuN-positive cells, even with Saturating concentrations of Sonic hedgehog (Shh), a potent GCP mitogen. However, these differentiation-promoting effects on GCPs are attenuated significantly in cells overexpressing a mutant JSAP1 that lacks the JNK-binding domain. Together, these data suggest that JSAP1 antagonizes the mitogenic effect of Shh on GCPs and promotes their exit front the cell cycle and differentiation, by modulating JNK activity. (c) 2008 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.mcn.2008.08.003

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  • Neural-specific ablation of the scaffold protein JSAP1 in mice causes neonatal death 査読

    Asuka Iwanaga, Tokiharu Sato, Kazushi Sugihara, Atsushi Hirao, Nobuyuki Takakura, Hiroshi Okamoto, Masahide Asano, Katsuji Yoshioka

    NEUROSCIENCE LETTERS   429 ( 1 )   43 - 48   2007年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    We previously identified c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as JNK-interacting protein 3) as a scaffolding factor for JNK intracellular signaling pathways. Targeted gene-disruption studies have shown that JSAP1 -null mice are unable to breathe and die shortly after birth. Although neural defects might be responsible for their death, there has been no convincing evidence for this. Here we first generated genetically engineered mice carrying a loxP-flanked (floxed) jsap1 gene. To evaluate the validity of this deletion as a jsap1 conditional knockout (KO), we created mice in which the same exon was deleted in all cell lineages, and compared their phenotypes with those of the jsapl conventional KO mice reported previously. The two KO lines showed indistinguishable phenotypes, i.e., neonatal death and morphological defects in the telencephalon, indicating that the conditional deletion was a true null mutation. We then introduced the floxed jsapl deletion mutant specifically into the neural lineage, and found that the jsapl conditional KO mice showed essentially the same phenotypes as the JSAP1-null mice. These results strongly suggest that the neonatal death of jsap1-deficient mice is caused by defects in the nervous system. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.neulet.2007.09.057

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  • Expression and distribution of JNK/SAPK-associated scaffold protein JSAP1 in developing and adult mouse brain. 査読

    Miura E, Fukaya M, Sato T, Sugihara K, Asano M, Yoshioka K, Watanabe M

    Journal of neurochemistry   97 ( 5 )   1431 - 1446   2006年6月

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  • Expression and distribution of JNK/SAPK-associated scaffold protein JSAP1 in developing and adult mouse brain 査読

    Eriko Miura, Masahiro Fukaya, Tokiharu Sato, Kazushi Sugihara, Masahide Asano, Katsuji Yoshioka, Masahiko Watanabe

    Journal of Neurochemistry   97 ( 5 )   1431 - 1446   2006年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The c-Jun N-terminal kinase (JNK) is one of the three major mitogen-activated protein kinases (MAPKs) playing key roles in various cellular processes in response to both extracellular and intracellular stimuli. JNK/SAPK-associated protein 1 (JSAP1 also referred to as JIP3) is a JNK-associated scaffold that controls the specificity and efficiency of JNK signaling cascades. Here we studied its expression in mouse brains. JSAP1 mRNA was expressed in developing and adult brains, showing spatial patterns similar to JNK1-3 mRNAs. In embryos, JSAP1 immunolabeling was intense for progenitor cells in the ventricular zone throughout the brain and in the external granular layer of the cerebellum, and for neurons and glial cells differentiating in the mantle zone. In adults, JSAP1 was distributed in various neurons and Bergmann glia, with higher levels in striatal cholinergic interneurons, telencephalic parvalbumin-positive interneurons and cerebellar Purkinje cells. In these neurons, JSAP1 was observed as tiny particulate staining in spines, dendrites, perikarya and axons, where it was often associated with the smooth endoplasmic reticulum (sER) and cell membrane. Immunoblots revealed enriched distribution in the microsomal fraction and cytosolic fraction. Therefore, the characteristic cellular expression and subcellular distribution of JSAP1 might be beneficial for cells to efficiently link external stimuli to the JNK MAPK pathway and other intracellular machineries. © 2006 International Society for Neurochemistry.

    DOI: 10.1111/j.1471-4159.2006.03835.x

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  • Expression and distribution of JNK/SAPK-associated scaffold protein JSAP1 in mouse brain 査読

    Miura Eriko, Fukaya Masahiro, Sato Tokiharu, Sugihara Kazushi, Asano Masahide, Yoshioka Katsuji, Watanabe Masahiko

    NEUROSCIENCE RESEARCH   55   S179   2006年

  • Impairment of cardiomyogenesis in embryonic stem cells lacking scaffold protein JSAP1 査読

    T Sato, K Hidaka, A Iwanaga, M Ito, M Asano, Y Nakabeppu, T Morisaki, K Yoshioka

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   338 ( 2 )   1152 - 1157   2005年12月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    We previously reported that c-Jun NH(2)-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1), a scaffold protein for JNK signaling, is important in embryonic stem (ES) cells during neurogenesis. In that study, we also observed the altered expression of mesodermal marker genes, which indicated that JSAP1 is involved in the differentiation of mesodermal lineages. Here, we investigated the function of JSAP1 in cardiomyocyte development using JSAP1-null ES cells, and found that cardiomyogenesis was impaired in the JSAP1-null mutant. The JSAP1 deficiency resulted in lower gene expression of the cardiac transcription factor Nkx2.5 and contractile proteins. In contrast, the mutant showed a significantly higher expression of mesoderm-related markers other than those of the cardiomyocyte lineage. Together, these results suggest that JSAP1 may be important for the differentiation of the mesodermal lineages, functioning as a positive factor for cardiomyocyte differentiation, and as an inhibitory factor for differentiation into other lineages. (c) 2005 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2005.10.052

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  • JSAP1/JIP3 cooperates with focal adhesion kinase to regulate c-Jun N-terminal kinase and cell migration 査読

    T Takino, M Nakada, H Miyamori, Y Watanabe, T Sato, D Gantulga, K Yoshioka, KM Yamada, H Sato

    JOURNAL OF BIOLOGICAL CHEMISTRY   280 ( 45 )   37772 - 37781   2005年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    c-Jun N-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1) ( also termed JNK-interacting protein 3; JIP3) is a member of a family of scaffold factors for the mitogen-activated protein kinase ( MAPK) cascades, and it also forms a complex with focal adhesion kinase (FAK). Here we demonstrate that JSAP1 serves as a cooperative scaffold for activation of JNK and regulation of cell migration in response to fibronectin (FN) stimulation. JSAP1 mediated an association between FAK and JNK, which was induced by either co-expression of Src or attachment of cells to FN. Complex formation of FAK with JSAP1 and p130 Crk-associated substrate (p130(Cas)) resulted in augmentation of FAK activity and phosphorylation of both JSAP1 and p130(Cas), which required p130(Cas) hyperphosphorylation and was abolished by inhibition of Src. JNK activation by FN was enhanced by JSAP1, which was suppressed by disrupting the FAK/p130(Cas) pathway by expression of a dominant-negative form of p130(Cas) or by inhibiting Src. We also documented the co-localization of JSAP1 with JNK and phosphorylated FAK at the leading edge and stimulation of cell migration by JSAP1 expression, which depended on its JNK binding domain and was suppressed by inhibition of JNK. The level of JSAP1 mRNA correlated with advanced malignancy in brain tumors, unlike other JIPs. We propose that the JSAP1 center dot FAK complex functions cooperatively as a scaffold for the JNK signaling pathway and regulator of cell migration on FN, and we suggest that JSAP1 is also associated with malignancy in brain tumors.

    DOI: 10.1074/jbc.M505241200

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  • Structure, regulation, and function of micro1 in the sea urchin Hemicentrotus pulcherrimus 査読

    Y Nishimura, T Sato, Y Morita, A Yamazaki, K Akasaka, M Yamaguchi

    DEVELOPMENT GENES AND EVOLUTION   214 ( 11 )   525 - 536   2004年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The animal-vegetal axis of sea urchin embryos is morphologically apparent at the 16-cell stage, when the mesomeres, macromeres, and micromeres align along it. At this stage, the micromere is the only autonomously specified blastomere that functions as a signaling center. We used a subtraction PCR survey to identify the homeobox gene micro1 as a micromere-specific gene. The micro1 gene is a representative of a novel family of paired-like class homeobox genes, along with PlHbox12 from Paracentrotus lividus and pmar1 from Strongylocentrotus purpuratus. In the present study, we showed that micro1 is a multicopy gene with six or more polymorphic loci, at least three of which are clustered in a 30-kb region of the genome. The micro1 gene is transiently expressed during early cleavage stages in the micromere. Recently, nuclear beta-catenin was shown to be essential for the specification of vegetal cell fates, including micromeres, and the temporal and spatial coincidence of micro1 expression with the nuclear entry of beta-catenin is highly suggestive. We demonstrated that micro1 is a direct target of beta-catenin. In addition, we showed that micro1 is necessary and sufficient for micromere specification. These observations on the structure, regulation, and function of micro1 lead to the conclusion that micro1 and pmar1 (and potentially PlHbox12) are orthologous.

    DOI: 10.1007/s00427-004-0442-0

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MISC

産業財産権

  • 情動障害の治療剤のスクリーニング方法

    善岡 克次, 吉原 亨, 佐藤 時春, 浅野 雅秀

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    出願番号:特願2010-208662  出願日:2010年9月

    公開番号:特開2011-089982 

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受賞

  • The 25th Annual Neuroscience Poster Session, 1st place prize

    2018年12月  

    佐藤 時春

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担当経験のある授業科目(researchmap)

  • 動物生理学実験

    機関名:金沢大学

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  • 分子生物学

    機関名:金沢大学

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