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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Adrenergic alpha-1 Receptor Agonists
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Adrenergic alpha-Agonists / pharmacology
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Animals
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GTP-Binding Protein alpha Subunits / physiology*
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GTP-Binding Protein alpha Subunits, G12-G13 / physiology
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GTP-Binding Protein alpha Subunits, Gi-Go / physiology
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GTP-Binding Protein alpha Subunits, Gq-G11 / physiology
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Genetic Vectors
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Guanine Nucleotide Exchange Factors / chemistry
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MAP Kinase Signaling System*
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Male
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Myocytes, Cardiac / drug effects
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Myocytes, Cardiac / enzymology*
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Myocytes, Cardiac / metabolism
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Pertussis Toxin / pharmacology
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Phenylephrine / pharmacology
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Protein Structure, Tertiary
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RGS Proteins / genetics
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RGS Proteins / metabolism
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Rats
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Rats, Wistar
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Receptor, Endothelin A / metabolism
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Receptors, Adrenergic, alpha-1 / metabolism
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Receptors, G-Protein-Coupled / metabolism*
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Receptors, Thrombin / metabolism
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Rho Guanine Nucleotide Exchange Factors
Substances
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Adrenergic alpha-1 Receptor Agonists
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Adrenergic alpha-Agonists
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GTP-Binding Protein alpha Subunits
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Guanine Nucleotide Exchange Factors
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RGS Proteins
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Receptor, Endothelin A
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Receptors, Adrenergic, alpha-1
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Receptors, G-Protein-Coupled
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Receptors, Thrombin
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Rho Guanine Nucleotide Exchange Factors
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RGS4 protein
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Phenylephrine
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Pertussis Toxin
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GTP-Binding Protein alpha Subunits, G12-G13
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GTP-Binding Protein alpha Subunits, Gi-Go
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GTP-Binding Protein alpha Subunits, Gq-G11