title: RGS2: a multifunctional regulator of G-protein signaling.
abstract: Regulators of G-protein signaling (RGS) proteins enhance the intrinsic rate at which certain heterotrimeric G-protein alpha-subunits hydrolyze GTP to GDP, thereby limiting the duration that alpha-subunits activate downstream effectors. This activity defines them as GTPase activating proteins (GAPs). As do other RGS proteins RGS2 possesses a 120 amino acid RGS domain, which mediates its GAP activity. In addition, RGS2 shares an N-terminal membrane targeting domain with RGS4 and RGS16. Found in many cell types, RGS2 expression is highly regulated. Functionally, RGS2 blocks Gq alpha-mediated signaling, a finding consistent with its potent Gq alpha GAP activity. Surprisingly, RGS2 inhibits Gs signaling to certain adenylyl cyclases. Like other RGS proteins, RGS2 lacks Gs alpha GAP activity, however it directly inhibits the activity of several adenylyl cyclase isoforms. Targeted mutation of RGS2 in mice impairs anti-viral immunity, increases anxiety levels, and alters synaptic development in hippocampal CA1 neurons. RGS2 has emerged as a multifunctional RGS protein that regulates multiple G-protein linked signaling pathways.
authors.affiliation: B-Cell Molecular Biology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. jkerhl@niaid.nih.gov
authors.forename: John H
authors.initials: JH
authors.lastname: Kehrl
authors.forename: Srikumar
authors.initials: S
authors.lastname: Sinnarajah
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D020710:RGS Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018035:Receptors, Odorant / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D020710:RGS Proteins; D018035:Receptors, Odorant; C105345:Rgs2 protein, mouse; D019204:GTP-Binding Proteins