A requirement for the rac1 GTPase in the signal transduction pathway leading to cardiac myocyte hypertrophy.

Journal Article (Journal Article)

We have used adenoviral-mediated gene transfer of a constitutively active (V12rac1) and dominant negative (N17rac1) isoform of rac1 to assess the role of this small GTPase in cardiac myocyte hypertrophy. Expression of V12rac1 in neonatal cardiac myocytes results in sarcomeric reorganization and an increase in cell size that is indistinguishable from ligand-stimulated hypertrophy. In addition, V12rac1 expression leads to an increase in atrial natriuretic peptide secretion. In contrast, expression of N17rac1, but not a truncated form of Raf-1, attenuated the morphological hypertrophy associated with phenylephrine stimulation. Consistent with the observed effects on morphology, expression of V12rac1 resulted in an increase in new protein synthesis, while N17rac1 expression inhibited phenylephrine-induced leucine incorporation. These results suggest rac1 is an essential element of the signaling pathway leading to cardiac myocyte hypertrophy.

Full Text

Duke Authors

Cited Authors

  • Pracyk, JB; Tanaka, K; Hegland, DD; Kim, KS; Sethi, R; Rovira, II; Blazina, DR; Lee, L; Bruder, JT; Kovesdi, I; Goldshmidt-Clermont, PJ; Irani, K; Finkel, T

Published Date

  • September 1, 1998

Published In

Volume / Issue

  • 102 / 5

Start / End Page

  • 929 - 937

PubMed ID

  • 9727061

Pubmed Central ID

  • PMC508958

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI2552


  • eng

Conference Location

  • United States