G(q) - and ras-dependent pathways mediate hypertrophy of neonatal rat ventricular myocytes following α1-adrenergic stimulation

V. J. LaMorte, J. Thorburn, D. Absher, A. Spiegel, J. H. Brown, K. R. Chien, J. R. Feramisco, K. U. Knowlton

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157 Scopus citations

Abstract

α1-Adrenergic agonists activate a hypertrophic response in cultured neonatal ventricular myocytes, which include an increase in cell size, organization of contractile proteins into sarcomeric units, and the induction of the atrial natriuretic factor (ANF) gene. Previous findings have supported a role for ras in this signaling pathway. Utilizing microinjection techniques to deliver affinity-purified neutralizing antibodies to Gα(q,11) into cultured ventricular myocytes, the current studies demonstrate a functional requirement for the heterotrimeric G protein, G(q), in the α1-adrenergic induction of the ANF gene, changes in cell size, organization of myofilaments, and phosphoinositide hydrolysis. Expression of a constitutively active mutant of Gα(q) leads to the expression of ANF protein in these cells. Taken together, these data suggest that G(q)-dependent pathways are necessary and sufficient to activate defined features of the hypertrophic response. In attempts to further delineate the relative roles of ras and G(q) in this pathway, we found that Gα(q) is required for α1-adrenergic phosphoinositide hydrolysis, though ras does not appear to be necessary for this response. In addition, we coexpressed an inhibitory ras mutant, along with the constitutively active Gα(q). Expression of ANF protein stimulated by the Gα(q) mutant was not inhibited. Thus, both ras- and G(q)-dependent pathways are necessary to fully transduce defined features of α1- adrenergic-stimulated hypertrophy of neonatal cardiac ventricular myocytes, but activated G(q) may be able to induce ANF expression independent of inhibitory ras.

Original languageEnglish (US)
Pages (from-to)13490-13496
Number of pages7
JournalJournal of Biological Chemistry
Volume269
Issue number18
StatePublished - Jan 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    LaMorte, V. J., Thorburn, J., Absher, D., Spiegel, A., Brown, J. H., Chien, K. R., Feramisco, J. R., & Knowlton, K. U. (1994). G(q) - and ras-dependent pathways mediate hypertrophy of neonatal rat ventricular myocytes following α1-adrenergic stimulation. Journal of Biological Chemistry, 269(18), 13490-13496.