Activation of ZAP-70 through specific dephosphorylation at the inhibitory Tyr-292 by the low molecular weight phosphotyrosine phosphatase (LMPTP).

The ZAP-70 protein-tyrosine kinase plays a central role in signaling from the T cell antigen receptor. Recruitment and activation of ZAP-70 are transient and are terminated by phosphorylation of negative regulatory tyrosine residues and dephosphorylation of positively acting sites. We report that the low molecular weight protein-tyrosine phosphatase (LMPTP) specifically ...
dephosphorylates the negative regulatory Tyr-292 of ZAP-70, thereby counteracting inactivation of ZAP-70. Expression of low levels of LMPTP resulted in increased ZAP-70 phosphorylation, presumably at the activating Tyr-493 and other sites, increased kinase activity, and augmented downstream signaling to the mitogen-activated protein kinase pathway. The ZAP-70 Y292F mutant was not affected by LMPTP. Our results indicate that LMPTP, like CD45, dephosphorylates a negative regulatory tyrosine site in a protein-tyrosine kinase and thereby strengthens T cell receptor signaling.
Mesh Terms:
Amino Acid Substitution, Animals, COS Cells, Cercopithecus aethiops, Cloning, Molecular, Enzyme Activation, Humans, Isoenzymes, Jurkat Cells, Mutagenesis, Site-Directed, Phosphotyrosine, Plasmids, Protein Tyrosine Phosphatases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Receptors, Antigen, T-Cell, Recombinant Fusion Proteins, Transfection, ZAP-70 Protein-Tyrosine Kinase
J. Biol. Chem.
Date: Jul. 05, 2002
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