Modulation of Titin-Based Stiffness in Hypertrophic Cardiomyopathy via Protein Kinase D.

ABSTRACT: The giant protein titin performs structure-preserving functions in the sarcomere and is important for the passive stiffness (F_passive) of cardiomyocytes. Protein kinase D (PKD) enzymes play crucial roles in regulating myocardial contraction, hypertrophy, and remodeling. PKD phosphorylates myofilament proteins, but it is not known whether the giant protein titin is also a PKD substrate. Here, we aimed to determine whether PKD phosphorylates titin and thereby modulates cardiomyocyte F_passive in normal and failing myocardium. The phosphorylation of titin was assessed in cardiomyocyte-specific PKD knock-out mice (cKO) and human hearts using immunoblotting with a phosphoserine/threonine and a phosphosite-specific titin antibody. PKD-dependent site-specific titin phosphoryl

SUBMITTER: Herwig M 

PROVIDER: S-EPMC7174613 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature