Direct Regulation of ZAP-70 by SHP-1 in T Cell Antigen Receptor Signaling

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Science  24 May 1996:
Vol. 272, Issue 5265, pp. 1173-1176
DOI: 10.1126/science.272.5265.1173


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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