Work

Distinct Tyrosine Phosphorylation Sites in ZAP-70 Mediate Activation and Negative Regulation of Antigen Receptor Function

Year: 1996

Type: article

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.

Source: Molecular and Cellular Biology

DOI: 10.1128/mcb.16.9.5026

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

Institutions: Howard Hughes Medical Institute, Washington University in St. Louis, University of Chicago, Wyeth

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases