Key result
Phosphorylation of the PEVK region of titin by protein kinase C α (PKCα) increases myocardial passive tension.
Highlights a novel mechanism whereby PKCα phosphorylates the PEVK region of titin, increasing myocardial passive stiffness.
Diastolic performance is regulated by net myocardial stiffness, which is determined by the mechano-sensitive protein network comprised of extracellular proteins such as collagen, intracellular sarcomeric proteins, and cell surface integrins. Mechanical force and its regulation are sensed and propagated by each of these components in a concerted fashion.1 During diastole, titin filaments serve as tensiometers and passive force generators. This is accomplished by modulation via directional signaling of multiple linkages between different regions within the titin molecule and the cellular contractile apparatus. An intricate network of signaling molecules coordinates the extracellular and intracellular components in the contraction of a sarcomere. In this issue of Circulation Research, Hidalgo and colleagues present an elegant set of experiments that reveal a novel mechanism whereby altering the phosphorylation state of titin modulates myocardial passive stiffness.2 Specifically, they demonstrated that titin, in addition to being a protein kinase A and protein kinase G substrate, is also a protein kinase C α (PKCα) substrate. They further identified the PEVK region of titin as the prominent site of PKCα phosphorylation, and showed that phosphorylation at this site increased passive tension.
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Ahmed et al. (2009) reported an editorial. PKCα phosphorylation of titin was evaluated on Myocardial passive tension. Phosphorylation of the PEVK region of titin by protein kinase C α (PKCα) increases myocardial passive tension.
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