title: Pericyte-specific expression of Rgs5: implications for PDGF and EDG receptor signaling during vascular maturation.
abstract: RGS proteins finely tune heterotrimeric G-protein signaling. Implying the need for such fine-tuning in the developing vascular system, in situ hybridization revealed a striking and extensive expression pattern of Rgs5 in the arterial walls of E12.5-E17.5 mouse embryos. The distribution and location of the Rgs5-positive cells typified that of pericytes and strikingly overlapped the known expression pattern of platelet-derived growth factor receptor (PDGFR)-beta. Both E14.5 PDGFR-beta- and platelet-derived growth factor (PDGF)-B-deficient mice exhibited markedly reduced levels of Rgs5 in their vascular plexa and small arteries. This likely reflects the loss of pericytes in the mutant mice. RGS5 acts as a potent GTPase activating protein for Gi(alpha) and Gq(alpha) and it attenuated angiotensin II-, endothelin-1-, sphingosine-1-phosphate-, and PDGF-induced ERK-2 phosphorylation. Together these results indicate that RGS5 exerts control over PDGFR-beta and GPCR-mediated signaling pathways active during fetal vascular maturation.
authors.affiliation: B-cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1876, USA.
authors.forename: Hyeseon
authors.initials: H
authors.lastname: Cho
authors.forename: Tohru
authors.initials: T
authors.lastname: Kozasa
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bondjers
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.forename: John H
authors.initials: JH
authors.lastname: Kehrl
mesh_terms: D016475:3T3 Cells; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D001158:Arteries / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D019332:Endothelin-1 / Q000037:antagonists & inhibitors; D017874:Immediate-Early Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D008246:Lysophospholipids; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D008954:Models, Biological; D020286:Pericytes / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic
chemical_list: D019332:Endothelin-1; D017874:Immediate-Early Proteins; D008246:Lysophospholipids; D010982:Platelet-Derived Growth Factor; D020710:RGS Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; C105346:Rgs5 protein, mouse; D000804:Angiotensin II; C060506:sphingosine 1-phosphate; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D019950:Mitogen-Activated Protein Kinase 1; D013110:Sphingosine