DIRECT REGULATION OF ZAP-70 BY SHP-1 IN T-CELL ANTIGEN RECEPTOR SIGNALING

The threshold at which antigen triggers lymphocyte activation is set b y the enzymes that regulate tyrosine phosphorylation. Upon T cell acti vation, the protein tyrosine phosphatase SHP-1 was found to bind to th e protein tyrosine kinase ZAP-70. This interaction resulted in an incr ease in SHP-1 phosphatase activity and a decrease in ZAP-70 kinase act ivity. Expression of a dominant negative mutant of SHP-1 in T cells in creased the sensitivity of the antigen receptor. Thus, SHP-1 functions as a negative regulator of the T cell antigen receptor and in setting the threshold of activation.