| Project/Area Number |
10670038
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | kanazawa University |
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Principal Investigator |
HASHII Minako Kanazawa Univ. Dept.Biophysical Genetics, Lecturer, 医学部, 講師 (10272957)
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| Co-Investigator(Kenkyū-buntansha) |
HOSHI Naoto Kanazawa Univ. Dept.Biophysical Genetics, Research Associate, 医学部, 助手 (90229170)
YOKOYAMA Shigeru Kanazawa Univ. Dept.Biophysical Genetics, Associate Professor, 医学部, 助教授 (00210633)
HIGASHIDA Haruhiro Kanazawa Univ. Dept.Biophysical Genetics, Professor, 医学部, 教授 (30093066)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Ras / Ca oscillation / Inositol tetrakisphosphate / Antisense / Bradykinin / Receptor-operated Ca influx / InsP4 receptor / Ras-GAP / InsP4 |
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| Research Abstract |
The final step is that GTP hydrolysis facilitated by GAP1 InsP_4 on c-Ras, but not on v-Ras, could lead to closing the channels. Such a molecular switch between activated and inactivated c-Ras may be a key to controling the Ca^<2+> influx channels in non-transformed fibroblast cells and this might be true in many other cells. In sharp contrast this regulation capacity for closing channels is lost in ras-transformed cells, so that v-Ras may cause Ca^<2+> influx channels to lock in the open state.
It is now generally accepted that GAP1 as an InsP_4-binding protein and Ras exchanger Sos activated by tyrosine kinases interact with Ras. Circumstantial evidence suggests that molecular association of these proteins seems to be involved in the opening and closing putative Ca^<2+> influx channels. Thus, Ca^<2+> influx machinery seems to be effectively controlled by two branches of signal transduction for tyrosine kinase activation and InsP_4 formation downstream of phospholipase C-coupled bradykinin receptors. This c-Ras-dependent Ca^<2+> influx in nontransformed cells provides a hint for identifying the action site of v-Ras, whose activation elicits repetitive [Ca^<2+>]i increases, called Ca^<2+> oscillations, in transformed cells. Our hypothesis may hold interest for the future design of anticancer drugs, because Ca^<2+> influx channels associated with Sos-GAP1-Ras could be a new target. Further validation is necessary to confirm our hypothesis by means of a technique which can functionally null each component in the Ca^<2+> influx process.
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