| Project/Area Number |
14580638
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional biochemistry
|
|---|
| Research Institution | HOKKAIDO UNIVERSITY |
|---|
Principal Investigator |
SHIMA Hiroshi Hokkaido Untv., Inst.Genet.Med., Asso.Prof., 遺伝子病制御研究所, 助教授 (10196462)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TANUMA Nobuhiro Hokkaido Untv., Inst.Genet.Med., Inst., 遺伝子病制御研究所, 助手 (40333645)
KIKUCHI Kunimi Hokkaido Untv., Inst.Genet.Med., Prof., 遺伝子病制御研究所, 教授 (20006117)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | phosphorylation / dephosphorylation / kinase / phosphatase / PP1 / tautomycetin / MARK / GSK3β / S6キナーゼ / raf / Aurora kinase / gsk3b / 細胞増殖 |
|---|
| Research Abstract |
In order to clarify regulation of translation by protein phosphorylation, we examined function of two protein phosphatases, PP1 and MKP-7 in cells.
1.Recently we found that tautomycetin/TC is an inhibitor of PP1. To examine whether TC inhibits PP1 in cultured cells, cells are treated with TC and then PP1 and PP2A activities in the cell extract were analyzed. TC was shown to inhibit PP1 completely without affecting PP2A in the cells.
2.When cells are treated with TC, MEK/ERK activation was inhibited. By co-expression of raf together with either wild type or inactive mutant type of PP1 catalytic subunit, we concluded that PP1 activity is necessary for activation of Raf/MEK/ERK pathway.
3. PP1 was shown to bind and negatively regulate Aurora kinases.
4.GSK3β was shown to associate with PP1/1-2 heterodimer and phosphorylate Thr72 of 1-2 in the cultured cells. It was suggested that GSK3β functions as molecular switch for PPIC by inactivating the inhibitory activity of 1-2 by phosphorylation
5.By two hybrid screening, PP1 catalytic subunit was identified as scapinin binding protein. It was suggested that PP1 is targeted to non-chromatin structure by scapinin, where it may function as a regulator of gene expression.
6.We newly identified a novel MAPK binding motif commonly conserved in MAPK phosphatases. MKP-7, a JNK specific phosphatase, was shown to be phosphorylated by ERK upon several stimuli.
|
