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(Circulation Research. 2005;96:711.)
© 2005 American Heart Association, Inc.

Editorials

Cardiac Hypertrophy Served With Protein Kinase C

Isoform Substitution Available at Additional Cost

Susan F. Steinberg, Mark A. Sussman

From the Department of Pharmacology (S.F.S.), Columbia University, New York, NY; and the Department of Biology (M.A.S.), San Diego State University, Calif.

Correspondence to Mark A. Sussman PhD, San Diego State University, SDSU Heart Institute, Department of Biology, NLS 426, 5500 Campanile Drive San Diego, CA 92182. E-mail sussman@heart.sdsu.edu

See related article, pages 748–755

Key Words: protein kinase C • hypertrophy • fibrosis • isoforms

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Pressure overload stimulation of the heart stimulates a medley of signaling leading to hypertrophic remodeling. This compensatory effort to increase cardiac output depends on harmonious blending of kinase activities. Participation of protein kinase C (PKC) isoforms in hypertrophic signaling following agonist stimulation or pressure overload is unequivocal, but teasing out the specific roles for various isoform subtypes has been a frustrating endeavor. Researchers have approached this issue by tinkering with PKC isoform kinase activities via overexpression, activating/interfering peptides, or creation of knockout mice.¹ Information gleaned from these studies has made 1 point abundantly clear: PKC isoforms have a propensity for shared activation stimuli and common substrate specificities. As such, altering the activity of 1 PKC isoform almost invariably has consequences for the expression/activation/localization of other family members that normally lead to coordinated PKC responses when the heart is subjected to stress. In the case of a study by Klein et al² in this issue, losing PKC prompts changes in PKC that spell bad news for cardiac structure and function.

Klein et al identify cross-regulation between the novel PKC and PKC isoforms in the heart. They demonstrate that PKC protein expression is similar in normal and knockout PKC^–/– mice under basal conditions and in normal hearts subjected to pressure overload, but that PKC protein expression and phosphorylation levels are increased in PKC^–/– hearts following pressure overload. Prior studies by other groups show that pressure overload-induced hypertrophy leaves PKC unaffected, whereas PKC phosphorylation as well as protein expression level are significantly increased.^3,4 . . . [Full Text of this Article]

Related Article:

Increased Collagen Deposition and Diastolic Dysfunction but Preserved Myocardial Hypertrophy After Pressure Overload in Mice Lacking PKC

Gunnar Klein, Arnd Schaefer, Denise Hilfiker-Kleiner, Dagmar Oppermann, Praphulla Shukla, Anja Quint, Eva Podewski, Andres Hilfiker, Frank Schröder, Michael Leitges, and Helmut Drexler
Circ. Res. 2005 96: 748-755. [Abstract] [Full Text] [PDF]

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