Raf-1: a novel cardiac troponin T kinase
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Phosphorylation of cardiac troponin is a key mechanism involved in regulation of contractile function. In vitro kinase assays revealed that lysates prepared from resting cardiomyocytes contain cardiac troponin I (cTnI) and cTnT kinase activity. cTnI phosphorylation is inhibited by pharmacologic inhibitors of PKA, PKC, Rho kinase and PKC effectors such as RSK and PKD; these kinase inhibitors do not inhibit phosphorylation of cTnT. Rather, cTnT phosphorylation is decreased by the Raf inhibitor GW5074. In vitro kinase assays show that recombinant Raf phosphorylates cTnT, and that Raf-dependent cTnT phosphorylation is abrogated by a T206E substitution; Raf does not phosphorylate cTnI. These studies identify Raf-dependent cTnT-Thr206 phosphorylation as a novel mechanism that would link growth factor-dependent signaling pathways to dynamic changes in cardiac contractile function.
KeywordsCardiac troponin T Raf-1 GW5074 Cardiomyocytes Phosphorylation
Protein kinase A
Protein kinase C
Protein kinase D
Phosphoinositide-dependent protein kinase
Apoptosis signal-regulating kinase-1
Ribosomal S6 kinase
This work was supported by United States Public Health Service—National Heart, Lung and Blood Institute grants HL-77860, HL-74161, and AHA-SDG 0335199 N.
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