| Project/Area Number |
14570287
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | Tokyo University of Science |
|---|
Principal Investigator |
FUSAKI Noemi FUSAKI,Noemi, 生命科学研究所, 助手 (40278635)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Keywords | SHP-1 / BCR / Actin / CD72 / ITIM / Lipid Raft / Tyrosine phosphatase / tyrosine phosphorylation / lipid raft |
|---|
| Research Abstract |
To elucidate the role of tyrosme-phosphatase SUP-1 in B cells, we have investigated new substrates of SUP-1, and identified actin and myosm as the substrates.These two proteins contained ITIMs and were tyrosine-phosphorylated after BCR stimulation.Hyper-phosphorylation of actin resulted in sustained actin polymerization in B cells expressing C/S SUP-1 mutant, suggesting that SUP-1 plays a pivotal role in reorganization of cytoskeletal architecture inducing acm dephophorylation.Furthermore, we also analyzed negative function of CD72, we had previously identified as a substrate of SUP-1.We generated ITIM mutants of CD72 and introduced into DT-4O cells that lacked chick homolog of CD72, CuB1 and ChB1r.N-ITIM mutant-expressing cells showed increased phophorylation of CD72 and NF-kB activation after BCR stimulation, indicating that lack of SUP-1 binding resulted in hyper-phosphorylation of Grb2-binding site and activation of NF-kB. We also found that CD72 was existed on lipid raft and palniitoylation of CD72 was important to its localization.
|
