Gq- and ras-dependent pathways mediate hypertrophy of neonatal rat ventricular myocytes following α1-Adrenergic stimulation

Vickie J. LaMorte, Jackie Thorburn, Devin Absher, Allen M. Spiegel, Joan Heller Brown, Kenneth R. Chien, James R. Feramisco, Kirk U. Knowlton

Research output: Contribution to journalArticle

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Abstract

α1-Adrenergic agonists activate a hypertrophie 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 Gαq,11 into cultured ventricular myocytes, the current studies demonstrate a functional requirement for the heterotrimeric G protein, Gq, 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 Gαq leads to the expression of ANF protein in these cells. Taken together, these data suggest that Gq-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 Gq in this pathway, we found that Gαq 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 Gαq. Expression of ANF protein stimulated by the Gαq mutant was not inhibited. Thus, both ras- and Gq-dependent pathways are necessary to fully transduce defined features of α1-adrenergic-stimulated hypertrophy of neonatal cardiac ventricular myocytes, but activated Gq 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 - May 6 1994
Externally publishedYes

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Atrial Natriuretic Factor
Adrenergic Agents
Muscle Cells
Hypertrophy
Rats
Phosphatidylinositols
Cell Size
Hydrolysis
Gq-G11 GTP-Binding Protein alpha Subunits
Genes
Heterotrimeric GTP-Binding Proteins
Contractile Proteins
Adrenergic Agonists
Myofibrils
Microinjections
Neutralizing Antibodies
Cardiac Myocytes
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

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

Gq- and ras-dependent pathways mediate hypertrophy of neonatal rat ventricular myocytes following α1-Adrenergic stimulation. / LaMorte, Vickie J.; Thorburn, Jackie; Absher, Devin; Spiegel, Allen M.; Brown, Joan Heller; Chien, Kenneth R.; Feramisco, James R.; Knowlton, Kirk U.

In: Journal of Biological Chemistry, Vol. 269, No. 18, 06.05.1994, p. 13490-13496.

Research output: Contribution to journalArticle

LaMorte, VJ, Thorburn, J, Absher, D, Spiegel, AM, Brown, JH, Chien, KR, Feramisco, JR & Knowlton, KU 1994, 'Gq- and ras-dependent pathways mediate hypertrophy of neonatal rat ventricular myocytes following α1-Adrenergic stimulation', Journal of Biological Chemistry, vol. 269, no. 18, pp. 13490-13496.
LaMorte, Vickie J. ; Thorburn, Jackie ; Absher, Devin ; Spiegel, Allen M. ; Brown, Joan Heller ; Chien, Kenneth R. ; Feramisco, James R. ; Knowlton, Kirk U. / Gq- and ras-dependent pathways mediate hypertrophy of neonatal rat ventricular myocytes following α1-Adrenergic stimulation. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 18. pp. 13490-13496.
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AU - Feramisco, James R.

AU - Knowlton, Kirk U.

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