Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling

DR Plas, R Johnson, JT Pingel, RJ Matthews, M Dalton… - Science, 1996 - science.org
DR Plas, R Johnson, JT Pingel, RJ Matthews, M Dalton, G Roy, AC Chan, ML Thomas
Science, 1996science.org
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 …
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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