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Description

Grb10 (insulin receptor-binding protein Grb-IR) is a ubiquitous adapter protein which is expressed in both fetal and adult tissues. It is a multidomain protein that interacts with a wide array of cellular targets, the PH domain allows interaction with several subtypes of phosphoinositides, the Ras-associating domain binds a wide variety of Ras GTPases, and the SH domain facilitates binding to membrane-bound tyrosine kinase receptors which link Grb10 to different signaling pathways. Most notably, Grb10 associates with the insulin receptor at phosphotyrosine residues via its C-terminal BPS (between PH and SH) domain and inhibits the enzymatic activity of the insulin receptor. Grb10 also acts downstream of the insulin receptor pathway to inhibit activation of AKT-1. In addition, Grb10 suppresses Wnt signalling by binding to the low-density lipoprotein receptor. In fetal tissues, Grb10 may play inhibit growth and placental size.