Dear Emmanuel,

The attached publication is concerned with cardiac failure, however, I believe that it might be helpful regarding another examples of markers.

Type 1 Phosphatase, a Negative Regulator of Cardiac Function

Andrew N. Carr,1 Albrecht G. Schmidt,1 Yoichi Suzuki,2 Federica del Monte,3 Yoji Sato,1,4

Carita Lanner,2 Kristine Breeden,2 Shao-Ling Jing,5 Patrick B. Allen,6 Paul Greengard,6

Atsuko Yatani,1 Brian D. Hoit,7 Ingrid L. Grupp,1 Roger J. Hajjar,3

Anna A. DePaoli-Roach,2 and Evangelia G. Kranias1

*

Increases in type 1 phosphatase (PP1) activity have been observed in end stage human heart failure, but the role of this enzyme in cardiac function is unknown. To elucidate the functional significance of increased PP1 activity, we generated models with (i) overexpression of the catalytic subunit of PP1 in murine hearts and (ii) ablation of the PP1-specific inhibitor. Overexpression of PP1 (threefold) was associated with depressed cardiac function, dilated cardiomyopathy, and premature mortality, consistent with heart failure. Ablation of the inhibitor was associated with moderate increases in PP1 activity (23%) and impaired -adrenergic contractile

responses. Extension of these findings to human heart failure indicated that the increased PP1 activity may be partially due to dephosphorylation or inactivation of its inhibitor. Indeed, expression of a constitutively active inhibitor was associated with rescue of -adrenergic responsiveness in failing human myocytes. Thus, PP1 is

an important regulator of cardiac function, and inhibition of its activity may represent a novel therapeutic target in heart failure.

To view the full publication, please see attached file.

Rafik

Hope you find some interesting substrates in the supplementary table of this paper-

http://www.sciencedirect.com/science/article/pii/S0968000410000460

Thank you everyone with your answers. I will keep you posted if we find a good substrate.