Regulation of the extracellular signal-regulated kinase pathway in adult myocardium: differential roles of G(q/11), G(i) and G(12/13) proteins in signalling by alpha(1)-adrenergic, endothelin-1 and thrombin-sensitive protease-activated receptors

A K Snabaitis, A Muntendorf, T Wieland, M Avkiran

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

Abstract

Using adenoviruses encoding RGS2, RGS4 and Lsc (regulator of G protein signalling (RGS) domain of p115 RhoGEF), we investigated the contributions of G(q/11), Gi and G(12/13) proteins to G protein-coupled receptor (GPCR)-mediated activation of the extracellular signal-regulated kinase (ERK) pathway in adult rat ventricular myocytes (ARVM). Exposure to phenylephrine, endothelin-1 (ET-1) or thrombin induced significant activation of ERK1/2 and their downstream target 90 kDa ribosomal S6 kinase (p90RSK), which was abolished by overexpression of RGS4 (inhibits signalling via G(q/11) and Gi) or RGS2 (inhibits signalling via G(q/11)). Pertussis toxin (inhibits signalling via Gi) only partially attenuated the activation of ERK1/2 and p90(RSK) by phenylephrine and ET-1, but abolished such activation by thrombin. Overexpression of Lsc (inhibits signalling via G(12/13)) did not affect the responses to phenylephrine and ET-1, but suppressed the activation of ERK1/2 and p90RSK by thrombin. We conclude that full activation of the ERK pathway in ARVM by alpha1-adrenergic, ET-1 and thrombin receptors requires the activation of distinct families of heterotrimeric G proteins.
Original languageEnglish
Pages (from-to)655 - 664
Number of pages10
JournalCellular Signalling
Volume17
Issue number5
DOIs
Publication statusPublished - May 2005

Fingerprint

Dive into the research topics of 'Regulation of the extracellular signal-regulated kinase pathway in adult myocardium: differential roles of G(q/11), G(i) and G(12/13) proteins in signalling by alpha(1)-adrenergic, endothelin-1 and thrombin-sensitive protease-activated receptors'. Together they form a unique fingerprint.

Cite this