THE ROLE OF TYROSINE KINASES AND PHOSPHOTYROSINE-CONTAINING RECOGNITION MOTIFS IN REGULATION OF THE T-CELL-ANTIGEN RECEPTOR-MEDIATED SIGNAL-TRANSDUCTION PATHWAY

T cell-mediated immune responses are initiated by interaction of antig en bound to a glycoprotein encoded by the major histocompatibility com plex with the T cell antigen receptor (TCR). These recognition and bin ding steps are followed by multiple intracellular biochemical events. The earliest event detected is an increase in intracellular protein ty rosine phosphorylation that involves a complex interaction of tyrosine kinases and phosphatases. Subsequently, one observes an increase in p rotein serine/threonine phosphorylation, phospholipid hydrolysis, and changes in intracellular Ca2+ levels. These and other biochemical chan ges lead to cell proliferation, differentiation, and acquisition of ef fector functions. While binding of extracellular growth factors to rec eptors containing cytoplasmic protein tyrosine kinase (PTK) domains in duces direct activation of their kinase activity, the multichain TCR l acks an intrinsic kinase domain and therefore represents a distinct ty pe of receptor. It transduces signals via the interaction with, and ac tivation of, nbn-receptor PTKs. Recent efforts directed at defining th e TCR-linked signaling pathways have provided insight into the regulat ory role of three PTKs, and the functional importance of some unique p rotein motifs in both TCR subunits and PTKs, which mediate critical pr otein-protein interactions in this pathway.