title: GIV/Girdin transmits signals from multiple receptors by triggering trimeric G protein activation.
abstract: Activation of trimeric G proteins has been traditionally viewed as the exclusive job of G protein-coupled receptors (GPCRs). This view has been challenged by the discovery of non-receptor activators of trimeric G proteins. Among them, GIV (a.k.a. Girdin) is the first for which a guanine nucleotide exchange factor (GEF) activity has been unequivocally associated with a well defined motif. Here we discuss how GIV assembles alternative signaling pathways by sensing cues from various classes of surface receptors and relaying them via G protein activation. We also describe the dysregulation of this mechanism in disease and how its targeting holds promise for novel therapeutics.
authors.affiliation: From the Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118 and mgm1@bu.edu.
authors.forename: Mikel
authors.initials: M
authors.lastname: Garcia-Marcos
authors.affiliation: the Departments of Medicine and prghosh@ucsd.edu.
authors.forename: Pradipta
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0651 mfarquhar@ucsd.edu.
authors.forename: Marilyn G
authors.initials: MG
authors.lastname: Farquhar
mesh_terms: D000818:Animals; D002465:Cell Movement; D002470:Cell Survival; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008938:Mitosis; D008958:Models, Molecular; D009362:Neoplasm Metastasis / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009404:Nephrotic Syndrome / Q000378:metabolism; D055503:Protein Multimerization; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: C502451:CCDC88A protein, human; D008840:Microfilament Proteins; D011956:Receptors, Cell Surface; D033921:Vesicular Transport Proteins; D019204:GTP-Binding Proteins
keywords: Guanine Nucleotide Exchange Factor (GEF); Heterotrimeric G Protein; Liver Fibrosis; Nephrotic Syndrome; Receptor Tyrosine Kinase; Src Homology 2 Domain (SH2 Domain); Tumor Metastasis