title: The aorta and heart differentially express RGS (regulators of G-protein signalling) proteins that selectively regulate sphingosine 1-phosphate, angiotensin II and endothelin-1 signalling.
abstract: Normal cardiovascular development and physiology depend in part upon signalling through G-protein-coupled receptors (GPCRs), such as the angiotensin II type 1 (AT(1)) receptor, sphingosine 1-phosphate (S1P) receptors and endothelin-1 (ET-1) receptor. Since regulator of G-protein signalling (RGS) proteins function as GTPase-activating proteins for the G alpha subunit of heterotrimeric G-proteins, these proteins undoubtedly have functional roles in the cardiovascular system. In the present paper, we show that human aorta and heart differentially express RGS1, RGS2, RGS3S (short-form), RGS3L (long-form), PDZ-RGS3 (PDZ domain-containing) and RGS4. The aorta prominently expresses mRNAs for all these RGS proteins except PDZ-RGS3. Various stimuli that are critical for both cardiovascular development and function regulate dynamically the mRNA levels of several of these RGS proteins in primary human aortic smooth muscle cells. Both RGS1 and RGS3 inhibit signalling through the S1P(1) (formerly known as EDG-1), S1P(2) (formerly known as EDG-5) and S1P(3) (formerly known as EDG-3) receptors, whereas RGS2 and RGS4 selectively attenuate S1P(2)-and S1P(3)-receptor signalling respectively. All of the tested RGS proteins inhibit AT(1)-receptor signalling, whereas only RGS3 and, to a lesser extent, RGS4 inhibit ET(A)-receptor signalling. The conspicuous expression of RGS proteins in the cardiovascular system and their selective effects on relevant GPCR-signalling pathways provide additional evidence that they have functional roles in cardiovascular development and physiology.
authors.affiliation: B-cell Molecular Immunology Section, Laboratory of Immunoregulation, Room 11B-08, Building 10, National Institute of Allergy and Infectious Diseases, 10 Center Drive, MSC 1876, National Institutes of Health, Bethesda, MD 20892-1876, USA.
authors.forename: Hyeseon
authors.initials: H
authors.lastname: Cho
authors.forename: Kathleen
authors.initials: K
authors.lastname: Harrison
authors.forename: Owen
authors.initials: O
authors.lastname: Schwartz
authors.forename: John H
authors.initials: JH
authors.lastname: Kehrl
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D001011:Aorta / Q000378:metabolism*; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D017931:DNA Primers; D019332:Endothelin-1 / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D019332:Endothelin-1; D008246:Lysophospholipids; D020710:RGS Proteins; D012333:RNA, Messenger; D000804:Angiotensin II; C060506:sphingosine 1-phosphate; D020928:Mitogen-Activated Protein Kinases; D013110:Sphingosine