title: Why does troponin I have so many phosphorylation sites? Fact and fancy.
abstract: We discuss a current controversy regarding the relative role of phosphorylation sites on cardiac troponin I (cTnI) (Fig. 1) in physiological and patho-physiological cardiac function. Studies with mouse models and in vitro studies indicate that multi-site phosphorylations are involved in both control of maximum tension and sarcomeric responsiveness to Ca(2+). Thus one hypothesis is that cardiac function reflects a balance of cTnI phosphorylations and a tilt in this balance may be maladaptive in acquired and genetic disorders of the heart. Studies on human heart samples taken mainly at end-stage heart failure, and in depth proteomic analysis of human and rat heart samples demonstrate that Ser23/Ser24 are the major and perhaps the only sites likely to be relevant to control cardiac function. Thus functional significance of Ser23/Ser24 phosphorylation is taken as fact, whereas the function of some other sites is treated as fancy. Maybe the extremes will meet: in any case we both agree that further work needs to be carried out with relatively large mammals and with determination of the time course of changes in phosphorylation to identify transient modifications that may be relevant at a beat-to-beat basis. Moreover, we agree that the changes and effects of cTnI phosphorylation need to be fully integrated into the effects of other phosphorylations in the cardiac myocyte.
authors.affiliation: Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, Center for Cardiovascular Research, Chicago, IL 60612, USA. solarorj@uic.edu
authors.forename: R John
authors.initials: RJ
authors.lastname: Solaro
authors.forename: Jolanda
authors.initials: J
authors.lastname: van der Velden
mesh_terms: D000818:Animals; D006801:Humans; D008954:Models, Biological; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D019210:Troponin I / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D019210:Troponin I; D010744:Phosphoric Monoester Hydrolases