| Project/Area Number |
02680151
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
代謝生物化学
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| Research Institution | National Institute of Neuroscience, NCNP |
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Principal Investigator |
HATTORI Seisuke Division of Biochem. and Cellular Biology, National Institute of Neuroscience, NCNP, 神経研究所, 室長 (50143508)
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| Co-Investigator(Kenkyū-buntansha) |
HOSHINO Masato Dept. of Pure and Applied Sciences, College of Arts and Sciences, University of, 教養学部, 助手 (40212196)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1990: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | PC12 / ras / NF1 / GAP / p21 / GTPase Activating Protein / Neurofibromatosis / P21 |
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| Research Abstract |
PC12 rat pheochromocytoma cells respond to NGF and undergo neuronal differentiation. Microinjection of antibody against ras oncogene product p21 inhibits NGF-dependent differentiation which indicates that ras function is essential for the differentiation. To study the molecular mechanism for the transduction of NGFinduced signals, we isolated several mutant cells which exhibit extremely low sensitivity to NGF. We are now trying to isolate gene (s) which rescue the mutated phenotype.
We analyzed the effect of various factors which make PC12 cells undergo the differentiation. Among them only NGF and epidermal growth factor (EGF) were shown to activate ras p21. Tyrosine kinase inhibitors blocked NGF-induced activation of ras p21, which suggested that tyrosine kinase activity may be essential for transduction of the signals evoked by NGF.
To characterize factors which modulate biochemical and enzymatic properties of ras gene product p21, we analyzed factors which stimulate intrinsic GTPase activity of ras p21. By this approach we identified the product of neurofibromatosis type I(NF1)gene whose loss of function may be involved in the onset of neurocutaneous disease, neurofibromatosis type I. NF1 gene product was located mainly in the particulate fraction. In contrast GTPase activating protein (GAP) mainly exists in the soluble fraction. Furthermore there found to be another factor with GTPase stimulating activity.
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