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  • Title: Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling.
    Author: Plas DR, Johnson R, Pingel JT, Matthews RJ, Dalton M, Roy G, Chan AC, Thomas ML.
    Journal: Science; 1996 May 24; 272(5265):1173-6. PubMed ID: 8638162.
    Abstract:
    The threshold at which antigen triggers lymphocyte activation is set by the enzymes that regulate tyrosine phosphorylation. Upon T cell activation, the protein tyrosine phosphatase SHP-1 was found to bind to the protein tyrosine kinase ZAP-70. This interaction resulted in an increase in SHP-1 phosphatase activity and a decrease in ZAP-70 kinase activity. Expression of a dominant negative mutant of SHP-1 in T cells increased 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.
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