T-CELL RECEPTOR-INDUCED PHOSPHORYLATION OF SOS REQUIRES ACTIVITY OF CD45, LCK, AND PROTEIN-KINASE-C, BUT NOT EPK

Stimulation of the T cell antigen receptor (TCR) activates signaling p athways involving protein kinases, phospholipase C gamma 1, and Has. H ow these second messengers interact to initiate distal activation even ts is an area of intense scrutiny, In this report, we confirm that TCR ligation results in phosphorylation of Sos, a guanine nucleotide exch ange factor for Has, This requires expression of both the CD45 tyrosin e phosphatase and the Lck protein tyrosine kinase and depends upon sig naling via protein kinase C. In contrast to previous studies examining requirements for Sos phosphorylation following insulin and epidermal growth factor receptor engagement, we show that TCR-induced phosphoryl ation of Sos does not require activation of the mitogen-activated prot ein kinase/extracellular signal regulated kinase (MEK/ERK) pathway, Ho wever, the basal phosphorylation of Sos in T cells is affected by eith er MEK or MEK-dependent kinases, Although Sos phosphorylation results in its dissociation from Grb2 following insulin stimulation in Chinese hamster ovary cells, TCR engagement on the Jurkat T cell line fails t o elicit a similar effect, These data demonstrate that the kinases res ponsible for Sos phosphorylation differ following ligation of various cell surface receptors and that the consequences of Sos phosphorylatio n relies, at Yeast in part, on sites of its phosphorylation.