Recent advances in lymphocyte signaling and regulation.

The antigen receptor signaling pathway in lymphocytes is vital to their development and biological function. Recent studies have shown that protein tyrosine kinases and phosphatases are essential components in this receptor signaling pathway and therefore, are critical for the development of mature and functionally competent lymphocytes. The Src kinase family of protein tyrosine kinases coordinates the early signaling events in antigen receptor signaling via phosphorylation of tyrosine-based substrates. These kinases are regulated by the concerted action of the Csk family of non-receptor protein tyrosine kinases and the protein tyrosine phosphatase, CD45. A complex set of phosphorylation and dephosphorylation events regulate protein tyrosine kinase activity. Upon antigen stimulation, Src protein tyrosine kinases in conjunction with the tyrosine kinases, ZAP-70 and Syk initiate downstream effectors leading to Ca2+ mobilization, the activation of the Ras pathway and transcriptional activation. The roles of the various adapter proteins in these pathways are now being elucidated. It is apparent that a network of phosphorylation events connect the antigen receptor to intracellular signaling pathways.