Distinct tyrosine phosphorylation sites in ZAP-70 mediate activation and negative regulation of antigen receptor function

Guanghui Kong, Mark Dalton, Juliane Bubeck Wardenburg, David Straus, Tomohiro Kurosaki, Andrew C. Chan

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Biochemical and genetic evidence has implicated two families of protein tyrosine kinases (PTKs), the Src-and Syk-PTKs, in T- and B-cell antigen receptor signaling. ZAP-70 is a member of the Syk-PTKs that associates with the T-cell antigen receptor and undergoes tyrosine phosphorylation following receptor activation. Three tyrosine residues, Tyr-292, -492, and -493, have been identified as sites of phosphorylation following T-cell antigen receptor engagement. Utilizing ZAP-70- and Syk-deficient lymphocytes (Syk- DT40 cells), we provide biochemical and functional evidence that heterologous trans-phosphorylation of Tyr-493 by a Src-PTK is required for antigen receptor-mediated activation of both the calcium and ras pathways. In contrast, cells expressing mutations at Tyr-292 or -492 demonstrate hyperactive T- and B-cell antigen receptor phenotypes. Thus, phosphorylation of ZAP-70 mediates both activation and inactivation of antigen receptor signaling.

Original languageEnglish
Pages (from-to)5026-5035
Number of pages10
JournalMolecular and cellular biology
Volume16
Issue number9
DOIs
StatePublished - 1996

Fingerprint

Dive into the research topics of 'Distinct tyrosine phosphorylation sites in ZAP-70 mediate activation and negative regulation of antigen receptor function'. Together they form a unique fingerprint.

Cite this