| Co-Investigator(Kenkyū-buntansha) |
SANO Kimihiko Kobe University, Faculty of Medicine, Assistant Professor, 医学部・附属病院, 講師 (40205993)
KAWAHARA Yasuhiro Kobe University, Faculty of Medicine, Assistant Professor, 医学部・附属病院, 講師 (80169755)
SASAKI Takuya Kobe University, Faculty of Medicine, Research Associate, 医学部, 助手 (40241278)
KIKUCHI Akira Kobe University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (10204827)
KAIBUCHI Kozo Kobe University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00169377)
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| Research Abstract |
There is the small GTP-binding protein (G protein) superfamily which consists of over fifty members. All members have monomeric proteins with Mrs between 20, 000 and 30, 000 which exhibit both GDP/GTP-binding and GTPase activities. In the present research project, we studied the functions and modes of activation of small G proteins and tried to prepare concerning cDNAs and antibodies as tools for certain diseases. Ras is the representative of this superfamily and is well known to regulate cell proliferation, differentiation, and transformation, but its modes of activation and action remain to be clarified. We characterized three GDP/GTP exchange proteins for Ras including Smg GDS, CDC25Mm, and mSos. We indentified a target protein for Ras and named it REKS, which phosphorylated MAP kinase kinase and thereby activated it in a Ras-dependent manner. Accumulating evidence suggests that Rho regulates certain functions through an actomyosin system. By use of C3 exoenzyme and Rho GDI, we showed that Rho regulated cell morphology, cell motility, membrane ruffling, cytokinesis, and smooth muscle contraction through an actomyosin system. Rab family is known to regulate intracellular vesicle transport, such as exocytosis, endocytosis, and transcytosis. Rab3A is a member of Rab family which is particularly implicated in neurotransmitter release from the synapse. We isolated the cDNA encoding a target protein for Rab3A, which selectively interacted with the GTP-bound form of Rab3A, and named it rabphilin-3A.These results suggest that small G proteins play crucial roles in various cell functions and that their cDNA and antibodies can be used at tools for diagnosis and treatment of certain diseases.
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