The project described in this application will focus the mechanisms by which ligation of the T-cell antigen receptor (TcR) and IL-2 receptor activate Ras GTPases in T cells. The downstream consequences of Ras activation, particularly IL-2 promoter activation, will also be investigated.
The specific aims of this application are: (1) to examine the roles of Shc, Grb2, and Crk adaptor proteins in receptor-mediated Ras activation, (2) to define the contributions of PKC-epsilon and phosphatidylcholine-specific phospholipase C (PC-PLC) to the activation of the Raf kinase in T cells, and (3) to determine whether Ras activation is involved in the downstream stimulation of JNKs by TcR and co-stimulatory signals.
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