TRANSMEMBRANE SIGNAL-TRANSDUCTION BY INTEGRIN CYTOPLASMIC DOMAINS EXPRESSED IN SINGLE-SUBUNIT CHIMERAS

Integrins are heterodimeric, transmembrane cell adhesion receptors tha t have recently been shown to function in transmembrane signal transdu ction. To examine the specific role of integrin intracellular domains in signal transduction, chimeric receptors containing various integrin intracellular domains coupled to a reporter consisting of the transme mbrane and extracellular domains of the small, non-signaling subunit o f the interleukin-2 receptor were expressed in cultured human fibrobla sts and assayed for their ability to trigger tyrosine phosphorylation of the 125-kDa cytoplasmic tyrosine kinase, pp125(FAK). Tyrosine phosp horylation of pp125(FAK) was induced in cultured fibroblasts that tran siently expressed chimeric receptors containing either the beta(1), be ta(3), beta(5) integrin intracellular domain and were selected by magn etic bead sorting. However, expression of chimeric receptors containin g either the alpha(5) or an alternatively spliced form of the beta(3) intracellular domain (beta(3B)), as well as those lacking an intracell ular domain, failed to induce tyrosine phosphorylation of pp125(FAK). These results indicate that information contained in the beta(1), beta (3), or beta(5) integrin intracellular domain is sufficient to stimula te integrin-mediated tyrosine phosphorylation of specific intracellula r proteins and that integrin extracellular and transmembrane domains a re not required for inducing tyrosine phosphorylation. Our results als o indicate that alternative splicing can regulate the ability of beta integrin intracellular domains to participate in signal transduction, and they further suggest that the carboxyl-terminal region of specific beta integrins may play a role in the signal transduction pathway inv olving extracellular matrix molecules.