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J. Biol. Chem., Vol. 278, Issue 36, 33694-33700, September 5, 2003

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Role of Troponin I Phosphorylation in Protein Kinase C-mediated Enhanced Contractile Performance of Rat Myocytes^*

Margaret V. Westfall  and Andrea R. Borton 

From the Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109-0686

Our goal was to define the role of phosphorylated cardiac troponin-I in the adult myocyte contractile performance response to activated protein kinase C. In agreement with earlier work, endothelin enhanced both adult rat myocyte contractile performance and cardiac troponin-I phosphorylation. Protein kinase C participated in both responses. The role of cardiac troponin-I phosphorylation in the contractile function response to protein kinase C was further investigated using gene transfer into myocytes of troponin-I isoforms/mutants lacking one or more phosphorylation sites previously identified in purified cardiac troponin-I. Sarcomeric replacement with slow skeletal troponin-I-abrogated protein kinase C-mediated troponin-I phosphorylation. In functional studies, endothelin slowed relaxation in myocytes expressing slow skeletal troponin-I, while the relaxation rate increased in myocytes expressing cardiac troponin-I. Based on these results, acceleration of myocyte relaxation during protein kinase C activation largely depended on cardiac troponin-I phosphorylation. Experiments with troponin-I isoform chimeras provided evidence that phosphorylation sites in the amino portion of cardiac troponin I-mediated the protein kinase C acceleration of relaxation. The cardiac troponin-I Thr-144 phosphorylation site identified in earlier biochemical studies was not significantly phosphorylated during the acute contractile response. Thus, amino-terminal protein kinase C-dependent phosphorylation sites in cardiac troponin-I are likely responsible for the accelerated relaxation observed in adult myocytes.

Received for publication, May 23, 2003 , and in revised form, June 11, 2003.

^* This work was supported by a McKay Grant from the University of Michigan, a Scientist Development grant from the American Heart Association, and the National Institutes of Health (to M. V. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Current address: Cell Signaling Technology, Inc., 166B Cummings Center, Beverly, MA 01915.

To whom correspondence should be addressed: Cardiac Surgery Section, University of Michigan, 1150 W. Medical Center Dr., B560 MSRBII, Ann Arbor, MI 48109-0686. Tel.: 734-615-8911; Fax: 734-763-0323; E-mail: wfall{at}umich.edu.

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