Coupling the TCR to downstream signalling pathways: The role of cytoplasmic and transmembrane adaptor proteins

Engagement of the T-cell receptor (TCR) complex initiates a cascade of intr acellular events ultimately leading to T-cell proliferation and differentia tion. One of the first detectable consequences of TCR triggering is the act ivation of cytoplasmic protein kinases which, through phosphorylation of sp ecific substrates, couple the TCR to downstream signalling cascades. Althou gh it is well established thai activation of the Ras- and the calcium-depen dent calcineurin pathway is required for the achievement of T-cell activati on, the precise mechanism as to how the TCR is connected to these intracell ular effector molecules is still unclear. Major progress has been made in t his regard. with the molecular characterization of novel cytoplasmic and tr ansmembrane molecules called adaptor proteins which integrate TCR-mediated signals at the intracellular level thus allowing fine tuning of T-cell resp onses. CELL SIGNAL 11;10:705-712, 1999. (C) 1999 Elsevier Science Inc.