Recent developments in lymphocyte activation: linking kinases to downstream signaling events.

Abstract

The past decade has witnessed major advances in our understanding of the molecular mechanisms that regulate lymphocyte activation. The observation that cytoplasmic protein tyrosine kinases (PTKs) are activated rapidly following ligation of lymphocyte antigen receptors provided a convenient starting point for investigators to begin to identify signaling intermediates in lymphocytes. It is now known that both conserved, ubiquitously expressed molecules and novel lymphocyte-specific proteins are substrates of these PTKs and that they regulate various signal transduction cascades. Among these substrates, the class of molecules known collectively as adapter proteins has emerged as an important component of several signaling cascades linking apical tyrosine kinases with more distal signaling pathways. This Perspective will focus on recent advances in our understanding of the role adapter proteins play in the integration of signals initiated by engagement of the T-cell receptor (TCR) for antigen.