Regulation of lymphocyte development and activation by the LAT family of adapter proteins

Transmembrane adapter proteins (TRAPs) are critical components of signaling pathways in lymphocytes, linking antigen receptor engagement to downstream cellular processes. While these proteins lack intrinsic enzymatic activity, their phosphorylation following receptor ligation allows them to function as scaffolds for the assembly of multi-molecular signaling complexes. Many TRAPs have recently been discovered, and numerous studies demonstrate their roles in the positive and negative regulation of lymphocyte maturation, activation, and differentiation. One such example is the linker for activation of T cells (LAT) family of adapter proteins. While LAT has been shown to play an indispensable role in T-cell and mast cell function, the other family members, linker for activation of B cells (LAB) and linker for activation of X cells (LAX), are necessary to fine-tune immune responses. In addition to its well-established role in the positive regulation of lymphocyte activation, LAT exerts an inhibitory effect on T-cell receptor-mediated signaling. Furthermore, LAT, along with LAB and LAX, plays a crucial role in establishing and maintaining tolerance. Here, we review recent data concerning the regulation of lymphocyte development and activation by the LAT family of proteins.