REGULATION OF LYMPHOCYTE FUNCTION BY PROTEIN-PHOSPHORYLATION

Variations in protein phosphorylation provide the predominant means of enzymatic regulation now known in biological systems, especially in the regulation of signal transduction from cell surface receptors. Analysis of these signaling pathways has proceeded especially rapidly in lymphocytes, in part because these cells can be isolated with relative ease and can in many cases be maintained in vitro for prolonged periods as clonal populations. During the past few years, both biochemical and genetic evidence has been adduced indicating that the antigen receptors of T and B lymphocytes associate functionally with nonreceptor protein tyrosine kinases. Similar data implicate protein tyrosine kinases in signaling from the CD4 and CD8 coreceptors and the beta chain of the IL-2 receptor. Protein serine/threonine kinases and several different phosphatases also participate in the intracellular propagation of antigen receptor-derived signals. Here we review the lymphocyte surface receptors that are believed to act by altering protein phosphorylation, the kinases and phosphatases that are believed to regulate signal transduction in lymphocytes, and the implications of these results for the broader study of cell signaling mechanisms.