JCB logo
Get More Out of Microscopy - Agilent iMIC 2000
  Home | Help | Feedback | Subscriptions | Archive | Search | Early Release Articles
Published online 25 February 2002. doi:10.1083/jcb.200108062
 The Rockefeller University Press, 0021-9525 $8.00
The Journal of Cell Biology
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Braz, J. C.
Right arrow Articles by Molkentin, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Braz, J. C.
Right arrow Articles by Molkentin, J. D.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Medline Plus Health Information
*Cardiomyopathy
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0021-9525
The Journal of Cell Biology

Article

 PKC{alpha} regulates the hypertrophic growth of cardiomyocytes through extracellular signal–regulated kinase1/2 (ERK1/2)

Julian C. Braz, Orlando F. Bueno, Leon J. De Windt and Jeffery D. Molkentin

Department of Pediatrics, University of Cincinnati, Children's Hospital Medical Center, Cincinnati, OH 45229

Address correspondence to Jeffery D. Molkentin, Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229-3039. Fax: (513) 636-5958. E-mail: jeff.molkentin{at}chmcc.org

Members of the protein kinase C (PKC) isozyme family are important signal transducers in virtually every mammalian cell type. Within the heart, PKC isozymes are thought to participate in a signaling network that programs developmental and pathological cardiomyocyte hypertrophic growth. To investigate the function of PKC signaling in regulating cardiomyocyte growth, adenoviral-mediated gene transfer of wild-type and dominant negative mutants of PKC{alpha}, ßII, {delta}, and {varepsilon} (only wild-type {zeta}) was performed in cultured neonatal rat cardiomyocytes. Overexpression of wild-type PKC{alpha}, ßII, {delta}, and {varepsilon} revealed distinct subcellular localizations upon activation suggesting unique functions of each isozyme in cardiomyocytes. Indeed, overexpression of wild-type PKC{alpha}, but not ßII, {delta}, {varepsilon}, or {zeta} induced hypertrophic growth of cardiomyocytes characterized by increased cell surface area, increased [3H]-leucine incorporation, and increased expression of the hypertrophic marker gene atrial natriuretic factor. In contrast, expression of dominant negative PKC{alpha}, ßII, {delta}, and {varepsilon} revealed a necessary role for PKC{alpha} as a mediator of agonist-induced cardiomyocyte hypertrophy, whereas dominant negative PKC{varepsilon} reduced cellular viability. A mechanism whereby PKC{alpha} might regulate hypertrophy was suggested by the observations that wild-type PKC{alpha} induced extracellular signal–regulated kinase1/2 (ERK1/2), that dominant negative PKC{alpha} inhibited PMA-induced ERK1/2 activation, and that dominant negative MEK1 (up-stream of ERK1/2) inhibited wild-type PKC{alpha}–induced hypertrophic growth. These results implicate PKC{alpha} as a necessary mediator of cardiomyocyte hypertrophic growth, in part, through a ERK1/2-dependent signaling pathway.

Key Words: cardiac; hypertrophic growth; protein kinase C; signal transduction; MAPK


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Early Release Articles