title: Novel bimodal effects of the G-protein tissue transglutaminase on adrenoreceptor signalling.
abstract: Tissue transglutaminase (tTG) is a novel G-protein that previous studies showed can couple ligand-bound activated alpha(1B) adrenoreceptors to phospholipase C-delta, resulting in phosphoinositide (PI) hydrolysis. In human neuroblastoma SH-SY5Y cells we found that although endogenous tTG can facilitate alpha(1B) adrenoreceptor-stimulated PI hydrolysis, its contribution is minor compared with the classical heterotrimeric G-protein G(q/11). Further, we show that the alpha(1B) adrenoreceptor recruits tTG to the membrane and that this recruitment is enhanced by agonist occupancy of the receptor. In addition, the effects of tTG on signalling are bimodal. At low expression levels, tTG enhanced alpha(1B) adrenoreceptor-stimulated PI hydrolysis, whereas at higher expression levels tTG attenuated significantly this response. These findings are the first to demonstrate that a protein can both facilitate and attenuate receptor-stimulated PI hydrolysis.
authors.affiliation: Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294-0017, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Tucholski
authors.forename: M
authors.initials: M
authors.lastname: Lesort
authors.forename: R S
authors.initials: RS
authors.lastname: Jope
authors.forename: G V
authors.initials: GV
authors.lastname: Johnson
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008563:Membrane Lipids / Q000378:metabolism; D009447:Neuroblastoma; D010656:Phenylephrine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D054799:Phospholipase C beta; D054803:Phospholipase C delta; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D011503:Transglutaminases / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: C547716:ADRA1B protein, human; D000316:Adrenergic alpha-Agonists; D007074:Immunoglobulin G; D007527:Isoenzymes; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins; D010656:Phenylephrine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D054803:Phospholipase C delta; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins