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Involvement of p21ras distinguishes positive and negative selection in thymocytes.
Author(s) -
Swan K.A.,
AlberolaIla J.,
Gross J.A.,
Appleby M.W.,
Forbush K.A.,
Thomas J.F.,
Perlmutter R.M.
Publication year - 1995
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1995.tb07001.x
Subject(s) - medical school , library science , medicine , medical education , computer science
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 p21ras in the control of thymocyte development, we generated mice expressing a dominant‐negative p21ras 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 p21ras 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 p21ras. 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 p21H‐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 p21H‐rasN17. These observations demonstrate that positive and negative selection, two conceptually antithetical consequences of TCR stimulation, are biochemically distinguishable.