title: Tuning the molecular giant titin through phosphorylation: role in health and disease.
abstract: Titin is a giant multi-functional filament that spans half of the sarcomere. Titin's extensible I-band region functions as a molecular spring that provides passive stiffness to cardiac myocytes. Elevated diastolic stiffness is found in a large fraction of heart failure patients and thus understanding the normal mechanisms and pathophysiology of passive stiffness modulation is clinically important. Here we provide first a brief general background on titin including what is known about titin isoforms and then focus on recently discovered post-translational modifications of titin that alter passive stiffness. We discuss the various kinases that have been shown to phosphorylate titin and address the possible roles of titin phosphorylation in cardiac disease, including heart failure with preserved ejection fraction (HFpEF).
authors.affiliation: Sarver Molecular Cardiovascular Research Program and the Department of Physiology, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Hidalgo
authors.forename: Henk
authors.initials: H
authors.lastname: Granzier
mesh_terms: D000818:Animals; D064211:Connectin / Q000737:chemistry / Q000378:metabolism*; D006331:Heart Diseases / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011487:Protein Conformation; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D016276:Ventricular Function
chemical_list: D064211:Connectin; D011494:Protein Kinases