ROLE OF TYROSINE KINASES IN LYMPHOCYTE-ACTIVATION

Interaction of T- and B-cell antigen receptors with cytoplasmic non-re ceptor tyrosine protein kinases is critical to the activation of lymph ocytes by antigen. Both the src-family tyrosine protein kinases Lck, F yn, Lyn and Blk and the syk-family tyrosine protein kinases Syk and ZA P-70 play a role in lymphocyte activation. The antigen receptors are c oupled to this cluster of kinases by the cytoplasmic tails of the gamm a, delta, epsilon, zeta, and eta subunits of the T-cell receptor, and the Ig-alpha and Ig-beta subunits of the B-cell receptor. Each of thes e proteins contains one or more 'tyrosine based activation motifs', wi th the amino acid sequence D/EX(7)D/EXXYXXL/IX(7)YXXL/I. This motif ap pears to allow binding of one or more src-like kinases, via their uniq ue amino termini, before the onset of lymphocyte activation. Invariant tyrosines in the motif become phosphorylated following the triggering of lymphocyte activation, and this modification induces the binding o f the src- and syk-family tyrosine protein kinases, and potentially ot her signalling molecules, through SH2 domains to the antigen receptors .