Modulation of TCR signaling by beta1 integrins: role of the tyrosine phosphatase SHP-1.
When cross-linked, beta1 integrins co-activate T cells together with a TCR-CD3 signal. Soluble anti-beta1 monoclonal antibodies, however, inhibit T cell activation. We report inhibition of early tyrosine kinases, including ZAP-70, p59(fyn), CD4-associated p56(lck) and TCR components under this condition. The tyrosine phosphatase SHP-1 is activated by engagement of beta1 integrins and is implicated in this negative regulation since no inhibition occurs in SHP-1 dominant-negative T cells. As shown by the use of Lck-deficient cells, the activation of the protein tyrosine phosphatase depends on a pool of p56(lck) that is not associated with CD4. These cross-talk events were also observed with the alpha4beta1 integrin ligand, VCAM-1. We propose that these results may be important in terms of lymphocyte circulation; while T cells migrate through the vascular endothelium, they are primed for an amplified response; as inflammation develops, a local accumulation of soluble integrin ligands may help to turn it off.
Mary
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INSERM U343 Hôpital de l'Archet, Nice, France.
Moon
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Venaille
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Thomas
M L
ML
Mary
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Bernard
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D017252:CD3 Complex / Q000276:immunology; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D017252:CD3 Complex; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D011948:Receptors, Antigen, T-Cell; D019010:Vascular Cell Adhesion Molecule-1; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases