The role of membrane-associated adaptors in T cell receptor signalling

Engagement of the T cell receptor lends to activation of several tyrosine k inases and phosphorylation of many intracellular;proteins. This is followed by Ca2+ mobilization and activation of multiple biochemical pathways, incl uding the Ras/MAPK cascade, and several downstream serine/ threonine kinase s. Membrane-associated adaptor proteins play an important role in T cell ac tivation by coupling TCR ligation at the membrane to distal signalling casc ades. Several new membrane associated adaptors have been identified in rece nt years. LAT (linker for activation of T cells) is an adaptor molecule, wh ich following its phosphorylation associates with Grb2, Gads, PLC-gamma 1, and other signalling molecules. The functional importance of this molecule has been demonstrated by the study of LAT-deficient cell lines and LAT-defi cient mice. Two other recently identified adaptor proteins, TRIM (T cell re ceptor interacting molecule) and SIT (SHP2-interacting transmembrane adapto r protein), which constitutively associate with several surface molecules, bind to PI3K and SHP2, respectively, after T cell activation and might also function in the TCR signalling pathway.