| Project/Area Number |
09672268
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | The Institute of Physical and Chemical Research (RIKEN) |
|---|
Principal Investigator |
FUJIOKA Toshiyuki (1998) RIKEN,Natori Special Laboratory, Resercher, 名取特別研究室, 研究員 (20133770)
櫨木 薫 (1997) 理化学研究所, 宇井特別研究室, 研究員 (50146007)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SEYA Tsukasa Osaka Medical Center for Cancer and Cardiovascular Diseases, Department of Cell, 研究所第6部, 室長(研究職) (10301805)
藤岡 聡之 理化学研究所, 宇井特別研究室, 研究員 (20133770)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
|---|
| Keywords | cellular signal transduction / tyrosine kinase / GTP-binding protein / epidermal growth factor / protein kinase C / phosphatidylinositol 3-kinase / cyclic AMP (cAMP) / Cbl / Fcレセプター |
|---|
| Research Abstract |
We have studied crosstalk between the tyrosine kinase system and the G-protein coupled system in cellular signal transduction. Our results suggest that there are crosstalks between the two systems and they are summarized as follows.
I.The crosstalk between the non-receptor tyrosine kinase system and the G-protein coupled system : It has been elucidated that protein kinase C (PKC) can modify the tyrosine kinase system activated by Fcgamma stimulation. PKC activated with phorbol ester, PMA, phosphorylates a protooncogene product, cCbl, resulting attenuation of the kinase activity of PKC by the tyrosine kinase associated with cCbl. Thus, cCbl is the key signal transduction molecule in the Fcgamma-related signal transduction in neutrophils.
II.The crosstalk between the receptor tyrosine kinase system and the G-protein coupled system : We have observed that IRS-1, IRS-2 and certain other proteins thus are tyrosine-phosphorylated by EGF, bound to the regulatory subunit (p85) of phosphatidylinositol (PI) 3-kinase, thereby activating the enzymic activity. Thus, EGF receptor-initiated signaling was mediated by PI 3-kinase associated with tyrosine-phosphorylated IRS, without involvement of insulin receptors, in short-term cultured rat hepatocytes. Furthermore, the magnitude of the activation of PI 3-kinase was augmented by the pretreatment of the cells with the cAMP-elevating agents such as glucagon. These results suggest that there is a crosstalk between the tyrosine kinase and G-protein coupled systems in hepatocytes.
|
