A novel function for the Tec family tyrosine kinase Itk in activation of beta 1 integrins by the T-cell receptor
| Autor: | Melody L. Woods, Yoji Shimizu, Avery August, Wendy J. Kivens, Yun Qiu, Margaret A. Adelsman |
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| Rok vydání: | 2001 |
| Předmět: |
CD3 Complex
Integrin Receptors Antigen T-Cell Biology SRC Family Tyrosine Kinase General Biochemistry Genetics and Molecular Biology Article Jurkat Cells Phosphatidylinositol 3-Kinases Phosphatidylinositol Phosphates Cell Adhesion Humans Src family kinase Molecular Biology General Immunology and Microbiology General Neuroscience Integrin beta1 Tumor Suppressor Proteins T-cell receptor PTEN Phosphohydrolase Protein-Tyrosine Kinases Actin cytoskeleton Actins Phosphoric Monoester Hydrolases Cell biology Cell Compartmentation Pleckstrin homology domain Protein Transport Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Cancer research biology.protein Signal transduction Tyrosine kinase Signal Transduction |
| Zdroj: | The EMBO journal. 20(6) |
| ISSN: | 0261-4189 |
| Popis: | Stimulation of T cells via the CD3--T-cell receptor (TCR) complex results in rapid increases in beta 1 integrin-mediated adhesion via poorly defined intracellular signaling events. We demonstrate that TCR-mediated activation of beta 1 integrins requires activation of the Tec family tyrosine kinase Itk and phosphatidylinositol 3-kinase (PI 3-K)-dependent recruitment of Itk to detergent-insoluble glycosphingolipid-enriched microdomains (DIGs) via binding of the pleckstrin homology domain of Itk to the PI 3-K product PI(3,4,5)-P(3). Activation of PI 3-K and the src family kinase Lck, via stimulation of the CD4 co-receptor, can initiate beta 1 integrin activation that is dependent on Itk function. Targeting of Itk specifically to DIGs, coupled with CD4 stimulation, can also activate beta 1 integrin function independently of TCR stimulation. Changes in beta 1 integrin function mediated by TCR activation of Itk are also accompanied by Itk-dependent modulation of the actin cytoskeleton. Thus, TCR-mediated activation of beta 1 integrins involves membrane relocalization and activation of Itk via coordinate action of PI 3-K and a src family tyrosine kinase. |
| Databáze: | OpenAIRE |
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