INHIBITION OF T-CELL ANTIGEN RECEPTOR SIGNALING BY OVEREXPRESSION OF P120GAP

T-cell antigen receptor triggering results in activation of protein ki nase C and mobilization of calcium. These two signals are necessary an d sufficient to activate the T-cell specific transcription factor NF-A T, which cooperates with other transcription factors activated by acce ssory signals to initiate expression of interleukin 2 and its receptor . The protein kinase C mediated pathway involves activation of ras pro teins. In a Jurkat cell model of T-cell activation, treatment with ant igen receptor agonists results in induction of expression of a reporte r gene under the control of a NF-AT dependent promoter. Overexpression of the ras GTPase activating protein p120GAP in these cells caused a significant inhibition of T-cell antigen receptor mediated induction, suggesting a role for p120GAP in regulation of ras. The inhibition was overcome by expression of a valine-12 mutant ras which lacks GTPase a ctivity.