title: Second messengers regulate RGS2 expression which is targeted to the nucleus.
abstract: Regulators of G-protein Signaling (RGS) proteins attenuate signaling activities of G proteins, and modulation of expression appears to be a primary mechanism for regulating RGS proteins. In human astrocytoma 1321N1 cells RGS2 expression was increased by activation of muscarinic receptors coupled to phosphoinositide signaling with carbachol, or by increased cyclic AMP production, demonstrating that both signaling systems can increase the expression of a RGS family member in a single cell type. Carbachol-stimulated increases in endogenous RGS2 protein levels appeared by immunocytochemical analysis to be largely confined to the nucleus, and this localization was confirmed by Western blot analysis which showed increased nuclear, but not cytosolic, RGS2 after carbachol treatment. Additionally, transiently expressed green fluorescent protein (GFP)-tagged, 6xHis-tagged, or unmodified RGS2 resulted in a predominant nuclear localization, as well as a distinct accumulation of RGS2 along the plasma membrane. The intranuclear localization of GFP-RGS2 was confirmed with confocal microscopy. Thus, RGS2 expression is rapidly and transiently increased by phosphoinositide signaling and by cyclic AMP, and endogenous and transfected RGS2 is largely, although not entirely, localized in the nucleus.
authors.affiliation: Department of Psychiatry and Behavioral Neurology, University of Alabama at Birmingham, 35294-0017, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Zmijewski
authors.forename: L
authors.initials: L
authors.lastname: Song
authors.forename: L
authors.initials: L
authors.lastname: Harkins
authors.forename: C S
authors.initials: CS
authors.lastname: Cobbs
authors.forename: R S
authors.initials: RS
authors.lastname: Jope
mesh_terms: D001254:Astrocytoma; D015153:Blotting, Western; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007545:Isoproterenol / Q000494:pharmacology; D018613:Microscopy, Confocal; D020710:RGS Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D015290:Second Messenger Systems / Q000502:physiology*; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D020710:RGS Proteins; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; C105345:Rgs2 protein, mouse; D005576:Colforsin; D002217:Carbachol; D000242:Cyclic AMP; D007545:Isoproterenol