Home LiteratureArticle Details

PMID: 9489702 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation.

Cell ·Vol. 92 ·No. 1 ·1998-01-09 ·Pages 83-92

Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE

Abstract

Despite extensive study, several of the major components involved in T cell receptor-mediated signaling remain unidentified. Here we report the cloning of the cDNA for a highly tyrosine-phosphorylated 36-38 kDa protein, previously characterized by its association with Grb2, phospholipase C-gamma1, and the p85 subunit of phosphoinositide 3-kinase. Deduced amino acid sequence identifies a novel integral membrane protein containing multiple potential tyrosine phosphorylation sites. We show that this protein is phosphorylated by ZAP-70/Syk protein tyrosine kinases leading to recruitment of multiple signaling molecules. Its function is demonstrated by inhibition of T cell activation following overexpression of a mutant form lacking critical tyrosine residues. Therefore, we propose to name the molecule LAT-linker for activation of T cells.

MeSH Terms

Adaptor Proteins, Signal Transducing Amino Acid Sequence Amino Acids/analysis Animals Carrier Proteins/genetics,isolation & purification,physiology Cell Line Cloning, Molecular DNA, Complementary/analysis,genetics Enzyme Precursors/metabolism GRB2 Adaptor Protein Humans Intracellular Signaling Peptides and Proteins Isoenzymes/metabolism Jurkat Cells/chemistry Lymphocyte Activation/physiology Membrane Proteins Molecular Sequence Data Phosphatidylinositol 3-Kinases/metabolism Phospholipase C gamma Phosphoproteins/genetics,isolation & purification,physiology Protein-Tyrosine Kinases/metabolism Proteins/metabolism Rats Receptors, Antigen, T-Cell/metabolism Sequence Homology, Amino Acid Signal Transduction/physiology Substrate Specificity Syk Kinase Tissue Distribution Type C Phospholipases/metabolism ZAP-70 Protein-Tyrosine Kinase

Chemicals

Adaptor Proteins, Signal Transducing Amino Acids Carrier Proteins DNA, Complementary Enzyme Precursors GRB2 Adaptor Protein GRB2 protein, human Grb2 protein, rat Intracellular Signaling Peptides and Proteins Isoenzymes LAT protein, human Membrane Proteins Phosphoproteins Proteins Receptors, Antigen, T-Cell Phosphatidylinositol 3-Kinases Protein-Tyrosine Kinases SYK protein, human Syk Kinase Syk protein, rat ZAP-70 Protein-Tyrosine Kinase ZAP70 protein, human Type C Phospholipases Phospholipase C gamma

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Zhang W

Section on Lymphocyte Signaling, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430, USA.

Sloan-Lancaster J

Kitchen J

Trible R P

Samelson L E

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(00)80901-0

Published

1998-01-09

Pages

83-92

Language

English

Region

United States

NLM ID

0413066

Subset

Databases

GENBANK

AF036905, AF036906, AF036907

External Links

PubMed source DOI: 10.1016/s0092-8674(00)80901-0 View journal details

Analysis Services

LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation.

Contact

WeChat Official Account