Control of TCR-mediated activation of beta 1 integrins by the ZAP-70 tyrosine kinase interdomain B region and the linker for activation of T cells adapter protein
| Autor: | Angie C. Quale, Yoji Shimizu, Alicia Felthauser, Seiji Goda, Melody L. Woods |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cytoplasm
T-Lymphocytes Immunology PTK2 Linker for Activation of T cells chemical and pharmacologic phenomena Protein tyrosine phosphatase Biology Receptor tyrosine kinase chemistry.chemical_compound Jurkat Cells Mice Phosphatidylinositol 3-Kinases Cell Adhesion Immunology and Allergy Animals Humans Tyrosine Phosphorylation Adaptor Proteins Signal Transducing ZAP-70 Protein-Tyrosine Kinase Phospholipase C gamma Integrin beta1 T-cell receptor Membrane Proteins hemic and immune systems Tyrosine phosphorylation Protein-Tyrosine Kinases Phosphoproteins Molecular biology Clone Cells Fibronectins Protein Structure Tertiary Up-Regulation Enzyme Activation Mice Inbred C57BL Adaptor Proteins Vesicular Transport chemistry Receptor-CD3 Complex Antigen T-Cell Type C Phospholipases Mutation biology.protein Carrier Proteins Proto-oncogene tyrosine-protein kinase Src Signal Transduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0022-1767 |
| Popis: | One of the earliest functional responses of T lymphocytes to extracellular signals that activate the Ag-specific CD3/TCR complex is a rapid, but reversible, increase in the functional activity of integrin adhesion receptors. Previous studies have implicated the tyrosine kinase ζ-associated protein of 70 kDa (ZAP-70) and the lipid kinase phosphatidylinositol 3-kinase, in the activation of β1 integrins by the CD3/TCR complex. In this report, we use human ZAP-70-deficient Jurkat T cells to demonstrate that the kinase activity of ZAP-70 is required for CD3/TCR-mediated increases in β1 integrin-mediated adhesion and activation of phosphatidylinositol 3-kinase. A tyrosine to phenylalanine substitution at position 315 in the interdomain B of ZAP-70 inhibits these responses, whereas a similar substitution at position 292 enhances these downstream signals. These mutations in the ZAP-70 interdomain B region also specifically affect CD3/TCR-mediated tyrosine phosphorylation of residues 171 and 191 in the cytoplasmic domain of the linker for activation of T cells (LAT) adapter protein. CD3/TCR signaling to β1 integrins is defective in LAT-deficient Jurkat T cells, and can be restored with expression of wild-type LAT. Mutant LAT constructs with tyrosine to phenylalanine substitutions at position 171 and/or position 191 do not restore CD3/TCR-mediated activation of β1 integrins in LAT-deficient T cells. Thus, these studies demonstrate that the interdomain B region of ZAP-70 regulates β1 integrin activation by the CD3/TCR via control of tyrosine phosphorylation of tyrosine residues 171 and 191 in the LAT cytoplasmic domain. |
| Databáze: | OpenAIRE |
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