Phosphotransfer reactions as a means of G protein activation.
Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) serve to transduce information from agonist-bound receptors to effector enzymes or ion channels. Current models of G protein activation-deactivation indicate that the oligomeric GDP-bound form must undergo release of GDP, bind GTP and undergo subunit dissociation, in order to be in active form (GTP bound alpha subunits and free beta gamma dimers) and to regulate effectors. The effect of receptor occupation by an agonist is generally accepted to be promotion of guanine nucleotide exchange thus allowing activation of the G protein. Recent studies indicate that transphosphorylation leading to the formation of GTP from GDP and ATP in the close vicinity, or even at the G protein, catalysed by membrane-associated nucleoside diphosphate kinase, may further activate G proteins. This activation is demonstrated by a decreased affinity of G protein-coupled receptors for agonists and an increased response of G protein coupled effectors. In addition, a phosphorylation of G protein beta subunits and consequent phosphate transfer reaction resulting in G protein activation has also been demonstrated. Finally, endogenously formed GTP was preferentially effective in activating some G proteins compared to exogenous GTP. The aim of this report is to present an overview of the evidence to date for a transphosphorylation as a means of G protein activation (see also refs [1 and 2] for reviews).
Piacentini
L
L
Innere Medizin III - Kardiologie, Universität Heidelberg, Germany.
Niroomand
F
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000502:physiology; D046911:Macromolecular Substances; D008954:Models, Biological; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism; D010455:Peptides; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction; D014862:Wasp Venoms / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D046911:Macromolecular Substances; D010455:Peptides; D011956:Receptors, Cell Surface; D014862:Wasp Venoms; D006153:Guanosine Diphosphate; C037500:mastoparan; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D009701:Nucleoside-Diphosphate Kinase; D019204:GTP-Binding Proteins