Sin: good or bad? A T lymphocyte perspective.

Stimulation of T cells through their antigen receptor induces a multitude of signaling networks that regulate T cell activation in the form of cytokine production and T cell proliferation. Multiple signal integration sites exist along these pathways in the form of multiprotein signaling complexes, the formation of which is facilitated by adapter and scaffold molecules. In recent years a number of adapter and scaffold molecules have been described in T cells and shown to play an integral part in T cell function. Among these molecules are proteins that function as positive or negative regulators of T cell activation downstream of the activated T cell receptor (TCR). Here, we discuss the role of a small family of multiadapter proteins on T cell activation, the p130Cas family, with emphasis on one of its members, Sin (Src-interacting protein). Our results suggest that Sin inhibits thymocyte development and T cell activation and is a novel negative regulator of T lymphocyte function.