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.
Keywords: Guanine Nucleotide Exchange Factor (GEF); Heterotrimeric G Protein; Liver Fibrosis; Nephrotic Syndrome; Receptor Tyrosine Kinase; Src Homology 2 Domain (SH2 Domain); Tumor Metastasis.
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.