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PMID: 8756661 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Molecular and cellular biology ·Vol. 16 ·No. 9 ·1996-09-00 ·Pages 5026-35

Kong G, Dalton M, Bubeck Wardenburg J, Straus D, Kurosaki T, Chan AC

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.

MeSH Terms
Amino Acid Sequence Animals Calcium/physiology Enzyme Precursors/deficiency,physiology Humans Intracellular Signaling Peptides and Proteins Leukemia-Lymphoma, Adult T-Cell/pathology Lymphocyte Activation Molecular Sequence Data Mutagenesis, Site-Directed Neoplasm Proteins/physiology Phosphorylation Phosphotyrosine/chemistry Protein Processing, Post-Translational Protein-Tyrosine Kinases/chemistry,deficiency,genetics,physiology Receptors, Antigen, T-Cell/physiology Signal Transduction Structure-Activity Relationship Syk Kinase Tumor Cells, Cultured ZAP-70 Protein-Tyrosine Kinase
Chemicals
Enzyme Precursors Intracellular Signaling Peptides and Proteins Neoplasm Proteins Receptors, Antigen, T-Cell Phosphotyrosine Protein-Tyrosine Kinases SYK protein, human Syk Kinase ZAP-70 Protein-Tyrosine Kinase ZAP70 protein, human Calcium
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kong G
Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Dalton M
Bubeck Wardenburg J
Straus D
Kurosaki T
Chan A C
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.16.9.5026
Published
1996-09-00
Pages
5026-35
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231504
Subset
IM
Grants
NIAMS NIH HHS · 5-T32-AR07279 · United States
NIGMS NIH HHS · 5T32GM07200 · United States
External Links
PubMed source DOI: 10.1128/MCB.16.9.5026 PMC Full Text View journal details
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