| Co-Investigator(Kenkyū-buntansha) |
KAWATA Masahito Kobe University, Faculty of Medicine, Research Associate, 医学部, 助手 (20224785)
KIKUCHI Akira Kobe University, Faculty of Medicine, Research Associate, 医学部, 助手 (10204827)
SANO Kimihiko Kobe University, Faculty of Medicine, Research Associate, 医学部, 助手 (40205993)
KAWAHARA Yasuhiro Kobe University, Faculty of Medicine, Research Associate, 医学部, 助手 (80169755)
KAIBUCHI Kozo Kobe University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00169377)
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| Research Abstract |
There is a superfamily of ras p21/ras p21-like small GTP-binding proteins (small G proteins) with GTPase activity. Over forty members have been reported, and all of them with Mrs between 20,000 and 41,000 are composed of a single respective polypeptide. Evidence is accumulating that small G proteins are involved in the regulation of cell growth and differentiation. In this research project, we have investigated the C-terminal structures of small G proteins, purified the regulatory proteins for small G proteins, and made monoclonal antibodies against small G proteins and their regulatory proteins. Most of small G proteins have the unique consensus C-terminal motifs containing at least one cysteine residue. We have found that the C-terminal systeine residues of smg p21B, rhoA p21, and smg p25A are geranylgeranylated, and that these prenylation are essential for each small G protein to bind to membranes. We have partially purified and characterized geranyl-geranyl transferase for rhoA p21
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from bovine brain. Small G proteins have two interconvertible forms, GDP-bound inactive and GTP-bound active forms. The conversion from the GDP-bound to GTP-bound form and the reverse conversion are induced by GDP/GTP exchange and GTPase reactions, respectively. We have purified and characterized several GDP/GTP exchange proteins (GDP dissociation stimulator (GDS) and GDP dissociation inhibitor (GDI)) and GTPase activating Proteins (GAP) for small G proteins. Among these regulatory proteins, we have cloned the cDNAs of smg p21 GDS, smg p25A GDI, and rho GDI, and made monoclonal antibodies against them. We have found that the levels of smg p21 mRNA increase in hematopoietic leukemiae cells after their differentiation into hematopoietic cells. We have also found that smg p25A is mainly detected inneural tissues by use of its specific monoclonal antibody, and that the levels of smg p25A mRNA increase in PC12 cells after their differentiation into neuron-like cells. These results suggest that smg p21 and smg p25A can be used as potential tumor markers for tumors derived from hematopoietic and neural tissues, respectively. Key Words : ras p21, small G proteins, Prenylation, GDP/GTP exchange protein, GTPase activating protein, Tumor markers. Less
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