Specific regulation of RGS2 messenger RNA by angiotensin II in cultured vascular smooth muscle cells

Sharon L. Grant, Bernard Lassègue, Kathy K. Griendling, Masuko Ushio-Fukai, P. Reid Lyons, R. Wayne Alexander

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

The effects of angiotensin II (Ang II) are mediated primarily by Ang II type 1 receptors, which in turn are coupled to heterotrimeric G proteins. After receptor activation, the G(α) and G(βγ) subunits dissociate, contributing to the signaling cascades involving protein kinase C (PKC) activation. Regulators of G protein signaling (RGS proteins) comprise a class of proteins that have been shown to negatively regulate the G(α) subunit. We examined which RGS sequences were expressed in vascular smooth muscle cells and which of these were regulated by Ang II. Reverse transcription-polymerase chain reaction showed that of 16 RGS sequences screened, six RGS transcripts (RGS2, 3, 10, 11, and 12 and GAIP) were present. Northern blot analysis demonstrated that RGS3, 10, and 12 and GAIP were not regulated by Ang II at the mRNA level. In contrast, RGS2 mRNA was rapidly and dose dependently increased (395 ± 24% peak, 45 min) by Ang II but returned to baseline level by 6 to 8 h. Phorbol-12-myristate-13-acetate, a PKC ctivator, robustly increased RGS2. This signal was attenuated by the PKC inhibitor GF 109203X (50 ± 4%) and by phorbol-12,13-dibutyrate-mediated down-regulation of PKC (48 ± 13%). Tyrosine kinase inhibition and calcium deprivation did not affect tie up-regulation of RGS2 mRNA after Ang II stimulation. Actinomycin D treatment inhibited both Ang II- and phorbol-12-myristate-13-acetate- stimulated RGS2 up-regulation, suggesting activation of transcription by these agonists. The stability of RGS2 mRNA did not appear to be affected by Ang II. Thus, RGS2 is a likely candidate for negative regulation of the G proteins coupled to the Ang II type 1 receptor in vascular smooth muscle cells. Regulation of this protein may be of critical importance in modulating the role of Ang II in vascular disease.

Original languageEnglish (US)
Pages (from-to)460-467
Number of pages8
JournalMolecular pharmacology
Volume57
Issue number3
DOIs
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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