Right time, right place: the organization of membrane proximal signaling

The basic mechanisms of lymphocyte activation are well established, with stimulation via the antigen receptor inducing a rapid wave of tyrosine phosphorylation that requires the coordinated action of multiple protein tyrosine kinase families. This in turn leads to the generation of second messengers like Ca2+, diacylglycerol (DAG) and inositoltrisphosphate (IP3) as well as the activation of effector molecules like Ras and the mitogen-activated protein kinases (MAPKs) and ultimately in activation of the transcription factors NFAT, AP-1, and NF-kappaB, resulting in gene transcription. Researchers, hoping to interconnect these events, have identified a multitude of proteins, among which is a relatively new group, the transmembrane adaptor proteins (TRAPs). TRAPs are unique in that they lack extracellular ligands and possess neither enzymatic nor transcriptional activity, but rather serve as scaffolds providing docking sites for other proteins and thereby serving to coordinate signals proximal to the membrane. Our study of these novel molecules is shedding new insights into the positive and negative regulatory mechanisms which fine tune antigen receptor signaling. (C) 2004 Elsevier Ltd. All rights reserved.