Alpha 4 beta 1 integrin-mediated tyrosine phosphorylation in human T cells: characterization of Crk- and Fyn-associated substrates (pp105, pp115, and human enhancer of filamentation-1) and integrin-dependent activation of p59fyn1.
Integrin adhesion receptors transduce signals that transmit information from the extracellular environment to the cell interior. Although integrins lack intrinsic tyrosine kinase activity, stimulation of the alpha 4 beta 1 integrin on human H9 T cells results in rapid tyrosine phosphorylation of proteins in the 105 to 115 kDa range. In this study, we report that alpha 4 integrin stimulation of H9 T cells results in tyrosine phosphorylation of three distinct proteins: pp105, pp115, and human enhancer of filamentation 1 (HEF1), all of which associate with the adapter protein c-Crk. However, pp115 can be distinguished from pp105 and HEF1 by its ability to associate with the SH2 domain of the tyrosine kinase p59fyn. Both pp105 and pp115 are antigenically distinct from HEF1, p130Cas, pp125FAK, Pyk2, p120cbl, and the p110 subunit of phosphatidylinositol 3-kinase. The functional significance of pp115 association with p59fyn is suggested by the ability of alpha 4 integrin stimulation to activate Fyn tyrosine kinase activity. These studies show that alpha 4 integrin stimulation of T cells results in the tyrosine phosphorylation of several distinct substrates. The association of these substrates with intracellular signaling intermediates, such as Crk and Fyn, may play a critical role in integrin-mediated regulation of T cell function.
Hunter
A J
AJ
Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis 55455, USA.
Shimizu
Y
Y
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules / Q000276:immunology; D002460:Cell Line; D004789:Enzyme Activation / Q000276:immunology; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008970:Molecular Weight; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl; D050737:Proto-Oncogene Proteins c-crk; D051076:Proto-Oncogene Proteins c-fyn; D011972:Receptor, Insulin / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D044767:Ubiquitin-Protein Ligases; D018909:src Homology Domains / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D016023:Integrins; C099942:NEDD9 protein, human; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D016201:Receptors, Lymphocyte Homing; D019000:Phosphotyrosine; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; C494957:FYN protein, human; D051417:Focal Adhesion Kinase 1; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D051076:Proto-Oncogene Proteins c-fyn; C067419:CBL protein, human