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or any given receptor, there are mechanisms that regulate the activation of signal transduction pathways, as well as mechanisms that extinguish those signaling pathways. Re- sponding to environmental signals requires that both posi- tive and negative regulation proceed in an ordered manner. Much research has focused on lymphocyte antigen receptor- induced signal transduction pathways, and an understanding of some of the initial events has been gained. The mecha- nisms that terminate signaling are equally important but less well understood. The inability to properly extinguish activa- tion cascades may result in inappropriate responses and per- haps even cell death. Concerning lymphocyte antigen receptors, antigen recognition results in the activation of intracellular protein tyrosine kinases, particularly members of the Src family kinases, as well as the ZAP-70/syk kinases. The key to antigen- induced signal transduction is the phosphorylation of crit- ical tyrosines within the cytoplasmic domains of the TCR

Of ITAMs and ITIMs: turning on and off the B cell antigen receptor.