2000 Fiscal Year Final Research Report Summary
Differential interaction of CrkII adaptor protein with plateletderived growth factor alpha-and beta-receptors is determined bu its internal tyrosine phosphorylation
| Project/Area Number |
11838002
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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 Institution | Chiba University |
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Principal Investigator |
MORI Seijiro Chiba University University Hospital, Lecturer, 医学部・附属病院, 講師 (50270848)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Yasushi Chiba University School of Medicine Professor, 医学部, 教授 (50101358)
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| Project Period (FY) |
1999 – 2000
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| Keywords | platelet-derived growth factor receptor / Crk / tyrosine phosphorylation |
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| Research Abstract |
CrkII is an intracellular adaptor protein involved in signal transduction by various growth factors. Activation of PDGF alpha-receptor resulted in its association with CrkII in vivo. In contrast, binding of CrkII to the PDGF beta-receptor was negligible, despite its becoming prominently phosphorylated. Bacterially expressed GST-CrkII SH2 domain specifically bound to Tyr-762 and Tyr-771 in the activated PDGF alpha-and beta-receptors, respectively. GST fusion protein of full-length CrkII also bound to the activated PDGF beta-receptor. However, tyrosine phosphorylation of GST-CrkII diminished its binding to the beta-receptor. CrkI, a truncated version of CrkII lacking the phosphorylatable tyrosine residue, could bind to both PDGF alpha-and beta-receptors in vivo. In conclusion, tyrosine phosphorylation of CrkII negatively affects its binding to the PDGF receptors. The differential binding of CrkII to the PDGF alpha-and beta-receptors may be a rationale for functional diversity between the two receptors.
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