摘要：

Receptor biologists have traditionally focused on receptors that are physiologically coupled to inductive responses such as gene expression, cytokinesis, secretion, or entry into the cell cycle. It has generally been assumed that such inductive responses were terminated by ligand decay or receptor desensitization, which lead to cessation of signaling. While such mechanisms are clearly operative, a number of recent experiments have demonstrated that inhibitory receptors exist that function to attenuate inductive signals and further indicate that these receptors play a very important regulatory role in biology. Relatively few inhibitory receptors have been defined in part because the effects of these receptors can only be detected against the backdrop of an inductive signal. However, this situation is rapidly changing as recent pioneering studies have provided new approaches to isolation of such receptors. Three reports published in recent months (1–3), one by Kubagawa et al. in the Proceedings (1), have identified two new extended families of cell surface proteins that may function as inhibitory receptors. These findings are discussed below in the context of known inhibitory receptors and their mode of action (Table 1). View this table: In this window In a new window Table 1 The growing inhibitory receptor family One of the first important insights regarding mechanisms of inhibitory signaling came from observations that signal transduction by tyrosine kinase-coupled receptors can be terminated by receptor association with phosphotyrosine phosphatases. A notable example is the termination of erythropoietin receptor signaling as a consequence of receptor phosphotyrosine binding to the hematopoietic lineage restricted phosphatase SHP-1 (previously known as HCP, SHPTP1, PTP1C, and SHP) (4). It was subsequently shown that FcγRIIB, a receptor for immunoglobulin G constant (Fc) regions known to mediate inhibition of antigen receptor activation of B cells, could recruit SHP-1 as well as the closely related and ubiquitiously expressed phosphotyrosine phosphatase SHP-2 (previously known as SHPTP2, PTP1D, and Syp) to the …

展开