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 α4β1 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 α4 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 α4 integrin stimulation to activate Fyn tyrosine kinase activity. These studies show that α4 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.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Immunology|
|State||Published - Nov 15 1997|