1998 Fiscal Year Final Research Report Summary
Crosstalk between tyrosine kinase and GTP-Binding Protein Systems in Cellular Signal Transduction
| Project/Area Number |
09672268
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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 |
Biological pharmacy
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| Research Institution | The Institute of Physical and Chemical Research (RIKEN) |
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Principal Investigator |
FUJIOKA Toshiyuki RIKEN,Natori Special Laboratory, Resercher, 名取特別研究室, 研究員 (20133770)
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| 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)
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| Project Period (FY) |
1997 – 1998
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| Keywords | cellular signal transduction / tyrosine kinase / GTP-binding protein / epidermal growth factor / protein kinase C / phosphatidylinositol 3-kinase / cyclic AMP (cAMP) / Cbl |
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| 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.
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Research Products
(13 results)
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[Publications] Asahi, K., Honma, Y., Hazeki, K., Sassa, T., Sakurai, A., and Takahashi, N.: "Cotylenin A,a plant-growth regulator induces the differentiation in murine and human myeloid luekemia cells." Biochem.Biophys.Res.Commun.238. 758-763 (1997)
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[Publications] Im, D., Fujioka, T., Katada, T., Kondo, M., Ui, M., and Okajima, F.: "Characterization of sphinegosine 1-phosphate-induced actions and its signaling pathways in rat hepatocytes." Am.J.Physiol.272. G1091-G1099 (1997)
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