| Project/Area Number |
10044239
|
|---|
| Research Category |
Grant-in-Aid for international Scientific Research
|
| Allocation Type | Single-year Grants |
|---|
| Section | Joint Research |
|---|
| Research Field |
Molecular biology
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
MORI Seijiro Chiba University School of Medicine Assistant, 医学部, 助手 (50270848)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HELLMAN Uif Ludwig Institute for Cancer Research, Associate
SAITO Yasushi Chiba University School of Medicine Professor, 医学部, 教授 (50101358)
HELLMAN Ulf.G.T. Ludwig Institute for Cancer Research Uppsala Branch Associate Member
HELLMAN Ulf Ludwig Institute for Cancer Research, Associate
|
|---|
| Project Period (FY) |
1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
|---|
| Keywords | receptor tyrosine kinase / polyubiquitination / ubiquitin protein ligase / ユピキチン |
|---|
| Research Abstract |
We have previously reported that most of the monomeric receptor tyrosine kinases undergo ligand-induced polyubiquitination and the ubiquitinated receptors are degraded by 26S proteasorne, and postulated that the ligand-induced receptor ubiquitination and subsequent its proteasomal degradation is a novel mechanism for down-regulation of signal transduction by the receptor tyrosine kinases, In the present study, we have tried to identify enzymatic components of a possible ubiquitination machinery, in order to clarify the molecular mechanism of the receptor ubiquitination. We have found that c-Cbl plays an important role in the ubiquitination process of the platelet-derived growth factor receptors ; c-Cbl binds to a carboxyl-terminal stretch of the PDGF beta-receptor, which have been previously identified by us as a recognition site of the ubiquitination system of enzymes ; the binding of c-Cbl to the receptor is necessary for the receptor ubiquitination ; v-Cbl dominant-negatively competes for the binding of c-Cbl to the receptor, thereby interferes with the receptor ubiquitination, resulting in acceleration of the receptor signaling. Our current study reveals for the first time the rn6lecular mechanism of the oncogenic effect of v-Cbl and, furthermore, provides the first crue to search for the enzymatic components of the ubiquitination system for receptor tyrosine kinases.
|
