title: Posttranslational modifications of cardiac troponin T: an overview.
abstract: Cardiac troponin (cTn) is an important sarcomeric protein complex situated on the thin filament and is involved in the regulation of cardiac muscle contraction. This regulation is primarily controlled by Ca(2+) binding to troponin C and in addition fine-tuned by the posttranslational modification of cTnI and cTnT. The vast majority of cTnT modifications involve the phosphorylation by protein kinase C (PKC) or other kinases and the N-terminal cleavage by caspase and calpain. In vitro studies employing reconstituted detergent-skinned fiber bundles and cell culture generally show a detrimental effect of cTnT phosphorylation on muscle contraction, which is backed by some in vivo studies finding increased cTnT phosphorylation in heart failure, but contradicted by others. In addition, N-terminal cleavage of cTnT is thought to be another factor influencing cardiac contraction. Time-dependent degradation of cTnT has been observed in human serum upon myocardial infarction. These molecular changes might influence the immunoreactivity of cTnT in the clinical immunoassay and have consequences for the clinical interpretations of these measurements. No consensus has yet been reached on the occurrence and extent of these observations and their underlying processes are subject of intense scientific debate. This review will focus on discussing these modifications, their implications on physiology and disease and summarizes the complex interplays of different enzymes on the molecular forms of cTnT and their associated effects.
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Streng
authors.forename: Douwe
authors.initials: D
authors.lastname: de Boer
authors.forename: Jolanda
authors.initials: J
authors.lastname: van der Velden
authors.forename: Marja P
authors.initials: MP
authors.lastname: van Dieijen-Visser
authors.forename: Will K W H
authors.initials: WK
authors.lastname: Wodzig
mesh_terms: D000818:Animals; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D020107:Troponin T / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020107:Troponin T
keywords: AMI; ASK1; Ca(2+)/calmodulin-dependent protein kinase II; CaMK II; Cardiac physiology; Cardiac troponin T; ESRD; Fragmentation; GFC; HF; LV; MS; P(i); PAK1/3; PKA/C/D; PP1; PP2A, protein phosphatase 1, 2A; PTM; Phosphorylation; ROCK-II; RV; Tm; acute myocardial infarction; apoptosis signal-regulating kinase 1; cTnT/I/C; cardiac troponin T, I, C; end-stage renal disease; gel filtration chromatography; heart failure; inorganic phosphate; left ventricle; mass spectrometry; p21 activated kinase 1, 3; posttranslational modification; protein kinase A, C, D; rho-A-dependent protein kinase; right ventricle; tropomyosin