HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 44, 41795-41801, November 1, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/44/41795    most recent M206744200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ward, D. G. Articles by Trayer, I. P. Search for Related Content PubMed PubMed Citation Articles by Ward, D. G. Articles by Trayer, I. P. Social Bookmarking                      What's this?

Structural Consequences of Cardiac Troponin I Phosphorylation^*

Douglas G. Ward, Michael P. Cornes, and Ian P. Trayer

From the School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom

-Adrenergic stimulation of the heart results in bisphosphorylation of the N-terminal extension of cardiac troponin I (TnI). Bisphosphorylation of TnI reduces the affinity of the regulatory site on troponin C (TnC) for Ca²⁺ by increasing the rate of Ca²⁺ dissociation. What remains unclear is how the phosphorylation signal is transmitted from one subunit of troponin to another. We have produced a series of mutations in the N-terminal extension of TnI designed to further our understanding of the mechanisms involved. The ability of phosphorylation of the mutant TnIs to affect Ca²⁺ sensitivity has been assessed. We find that the Pro residues found in a conserved (Xaa-Pro)₄ motif N-terminal to the phosphorylation sites are not required for the effect of the N-terminal extension on Ca²⁺ binding in the presence or absence of phosphorylation. Our experiments also reveal that the full effects of phosphorylation are seen even when residues 1-15 of TnI are deleted. If further residues are removed, not only does the effect of phosphorylation diminish but deletion of the N-terminal extension mimics phosphorylation. We propose that TnI residues 16-29 bind to TnC stabilizing the "open" Ca²⁺-bound state. Phosphorylation (or deletion) prevents this binding, accelerating Ca²⁺ release.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Sadayappan, N. Finley, J. W. Howarth, H. Osinska, R. Klevitsky, J. N. Lorenz, P. R. Rosevear, and J. Robbins Role of the acidic N' region of cardiac troponin I in regulating myocardial function FASEB J, April 1, 2008; 22(4): 1246 - 1257. [Abstract] [Full Text] [PDF]

				J. P. Davis and S. B. Tikunova Ca2+ exchange with troponin C and cardiac muscle dynamics Cardiovasc Res, March 1, 2008; 77(4): 619 - 626. [Abstract] [Full Text] [PDF]

				W.-J. Dong, J. Xing, Y. Ouyang, J. An, and H. C. Cheung Structural Kinetics of Cardiac Troponin C Mutants Linked to Familial Hypertrophic and Dilated Cardiomyopathy in Troponin Complexes J. Biol. Chem., February 8, 2008; 283(6): 3424 - 3432. [Abstract] [Full Text] [PDF]

				M. V. Westfall, A. M. Lee, and D. A. Robinson Differential Contribution of Troponin I Phosphorylation Sites to the Endothelin-modulated Contractile Response J. Biol. Chem., December 16, 2005; 280(50): 41324 - 41331. [Abstract] [Full Text] [PDF]

				J. C. Barbato, Q.-Q. Huang, M. M. Hossain, M. Bond, and J.-P. Jin Proteolytic N-terminal Truncation of Cardiac Troponin I Enhances Ventricular Diastolic Function J. Biol. Chem., February 25, 2005; 280(8): 6602 - 6609. [Abstract] [Full Text] [PDF]