title: Molecular and integrated biology of thin filament protein phosphorylation in heart muscle.
abstract: An increasing body of evidence points to posttranslational modifications of the thin filament regulatory proteins, cardiac troponin T (cTnT) and cardiac troponin I (cTnI) by protein kinase C (PKC) phosphorylation as important in both long- and short-term regulation of cardiac function and potentially implicated in the transition between compensated hypertrophy and decompensation. The main sites for PKC-dependent phosphorylation on cTnI are Ser43, Ser45, and Thr144 and on cTnT are Thr197, Ser201, Thr206, and Thr287 (mouse sequence). We analyzed the function of each phosphorylation residue using a phosphorylation mimic approach introducing glutamates (E) at PKC phosphorylation sites and then measuring the isometric tension of fiber bundles exchanged with these mutants. We also directly phosphorylated cTnI and cTnT by PKC, incorporated the phosphorylated troponins in the myofilament lattice, and determined the isometric tension at varying Ca(2+) concentrations. We followed the experimental data with computational analysis prediction of helical content of cTnI and cTnT peptides that undergo phosphorylation. Here we summarize our recent data on the specific functional role of PKC phosphorylation sites of cTnI and cTnT.
authors.affiliation: Department of Physiology and Biophysics, Program in Cardiovascular Sciences, College of Medicine, University of Illinois at Chicago, 60612, USA.
authors.forename: Marius P
authors.initials: MP
authors.lastname: Sumandea
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Burkart
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Pieter P
authors.initials: PP
authors.lastname: De Tombe
authors.forename: R John
authors.initials: RJ
authors.lastname: Solaro
mesh_terms: D000595:Amino Acid Sequence; D003902:Detergents; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011487:Protein Conformation; D011493:Protein Kinase C / Q000378:metabolism; D019210:Troponin I / Q000737:chemistry / Q000502:physiology*; D020107:Troponin T / Q000737:chemistry / Q000502:physiology*
chemical_list: D003902:Detergents; D019210:Troponin I; D020107:Troponin T; D011493:Protein Kinase C