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| INVOLVEMENT OF P21(RAS) DISTINGUISHES POSITIVE AND NEGATIVE SELECTION IN THYMOCYTES |
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| Author(s): SWAN KA, ALBEROLAILA J, GROSS JA, APPLEBY MW, FORBUSH KA, THOMAS JF, PERLMUTTER RM |
| Source: EMBO JOURNAL Volume: 14 Issue: 2 Pages: 276-285 Published: JAN 16 1995 |
| Times Cited: 230 References: 85 |
| Abstract: Small molecular weight GTP binding proteins of the ras family have been implicated in signal transduction from the T cell antigen receptor (TCR), To test the importance of p21(ras) in the control of thymocyte development, we generated mice expressing a dominant-negative p21(ras) protein (H-rasN17) in T lineage cells under the control of the lck proximal promoter, Proliferation of thymocytes from lck-H-rasN17 mice in response to TCR stimulation was nearly completely blocked, confirming the importance of p21(ras) in mediating TCR-derived signals in mature CD4(+)8(-) or CD8(+)4(-) thymocytes. In contrast, some TCR-derived signals proceeded unimpaired in the CD4(+)8(+) thymocytes of mice expressing dominant-negative p21(ras). Analysis of thymocyte development in mice made doubly transgenic for the H-Y-specific TCR and lck-H-rasN17 demonstrated that antigen-specific negative selection occurs normally in the presence of p21(H-rasN17). Superantigen-induced negative selection in vivo also proceeded unhindered in H-rasN17 thymocytes, In contrast, positive selection of thymocytes in the H-Y mice was severely compromised by the presence of p21(H-rasN17). These observations demonstrate that positive and negative selection, two conceptually antithetical consequences of TCR stimulation, are biochemically distinguishable. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV WASHINGTON, SCH MED, HOWARD HUGHES MED INST, SEATTLE, WA 98195 USA
2. UNIV WASHINGTON, SCH MED, DEPT IMMUNOL, SEATTLE, WA 98195 USA
3. UNIV WASHINGTON, SCH MED, DEPT BIOCHEM, SEATTLE, WA 98195 USA
4. UNIV WASHINGTON, SCH MED, DEPT MED, SEATTLE, WA 98195 USA |
| Publisher: OXFORD UNIV PRESS UNITED KINGDOM, WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: QD399 |
| ISSN: 0261-4189 |
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