Molecular mechanisms of lymphocyte proliferation during the development
| Project/Area Number |
09470093
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
MINATO Nagahiro Kyoto University.Dept.of.Immunol.Prof., 医学研究科, 教授 (40137716)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IWAI Kazuhiro Kyoto University.Dept.of.Immunol.Assist.Prof., 医学研究科, 助教授 (60252459)
HATTORI Masakazu Kyoto University.Dept.of.Immunol.Assist.Prof., 医学研究科, 助教授 (40211479)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
|
| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 1998: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1997: ¥9,900,000 (Direct Cost: ¥9,900,000)
|
|---|
| Keywords | Small GTPases / Rap 1 / Ras / Cytaskleton / Signal transduction / Antigen receptors / Immune response / GTPase activating protain(GAP) / アナ-ジ- / バキュロウイルス / 低分子量G蛋白 / クローン増巾 / GTPase活性化蛋白 |
|---|
| Research Abstract |
We have isolated a new gene termed Spa-I that is predominantly expressed in the Iymphohematopoietic tissues, and indicated that Spa-I encodes a protein SPA-I which exhibits specific GTPase-activating activity (GAP) for Ras-related small GTPase Rap1 in vitro. In the present study, we have proved that SPA-l indeed exhibits Rap1 GAP activity in the cells, counteracting the GDP/GTP exchanger activity of C3G for Rapt. Transfection experiments indicated that overexpression of SPA-I induced cell rounding and detachment, while C3G overexpression resulted in the enlargement and extensive spreading of cells, strongly suggesting that SPA-I controls cell morphology and adherence via regulation of Rapt. SPA-I was shown to be associated with cytoskeleton in the cells. In lymphocytes, SPA-I also regulates Rap1 activation downstream of antigen receptors. By using antigen specific T cell clones, it has been indicated that Rapl is activated by antigenic stimulation in a distinct kinetics with Ras. Furthermore, Rap1 was activated selectively by the suboptimal stimulation in the absence of co-receptor engagement, while Ras was activated only in the presence of co-receptor engagement. The activation of Rapl in the optimal antigenic stimulation was strongly suggested to be suppressed by the activation of SPA-1. These results have strongly suggested that Rapl mediates a distinct, possibly compensatory signals from Ras downstream of antigen receptors. To gain the distinct insights for the enigmatic Rapl and SPA-1 in the immunological responsiveness of lymphocytes, we have recently succeeded in establishing Spa-1 gene-targeted mice. Analysis of immune responsiveness in such mice should help to understand the roles Rapl and Spa-I play in vivo.
|
Report
(3 results)
Research Products
(23 results)
