Non-canonical functions of RGS proteins

Regulators of G protein signalling (RCS) proteins are united into a family by the presence of the RGS domain which serves as a GTPase-activating protein (GAP) for various Galpha subunits of heterotrimeric G proteins. Through this mechanism. RCS proteins regulate signalling of numerous G protein-coupled receptors. In addition to the RCS domains, RCS proteins contain diverse regions of various lengths that regulate intracellular localization. GAP activity or receptor selectivity of RCS proteins, often through interaction with other partners. However, it is becoming increasingly appreciated that through these non-RCS regions. RCS proteins can serve non-canonical functions distinct from inactivation of Galpha subunits. This review summarizes the data implicating RGS proteins in the (i) regulation of G protein signalling by non-canonical mechanisms, (ii) regulation of non-G protein signalling, (iii) signal transduction from receptors not coupled to G proteins, (iv) activation of mitogen-activated protein kinases, and (v) non-canonical functions in the nucleus. (C) 2010 Elsevier Inc. All rights reserved.