title: Heart failure-specific changes in protein kinase signalling.
abstract: Among the myriad of molecular alterations occurring in heart failure development, aggravation of the disease is often attributed to global or local changes in protein kinase activity, thus making protein kinases attractive targets for therapeutic intervention. Since protein kinases do not only have maladaptive roles, but also contribute to the physiological integrity of cells, it is a challenging task to circumvent undesired inhibition of protein kinase activity. Identification of posttranslational modifications and/or protein-protein interactions that are exclusively apparent under pathophysiological conditions provides exciting information for alternative non-kinase inhibitory treatment strategies that eliminate maladaptive functions of a protein kinase, but preserve the beneficial ones. Here, we focus on the disease-specific regulation of a number of protein kinases, namely, Ca(2+)/calmodulin-dependent protein kinase II isoform δ (CaMKIIδ), G protein-coupled receptor kinase 2 (GRK2), extracellular signal-regulated kinase 1 and 2 (ERK1/2), protein kinase D (PKD) and protein kinase C isoform β2 (PKCβ2), which are embedded in complex signal transduction pathways implicated in heart failure development, and discuss potential avenues for novel treatment strategies to combat heart disease.
authors: Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Strasse 9, 97078, Würzburg, Germany, Lorenz@toxi.uni-wuerzburg.de.
authors: Kristina
authors: K
authors: Lorenz
authors: Konstantina
authors: K
authors: Stathopoulou
authors: Evelyn
authors: E
authors: Schmid
authors: Petra
authors: P
authors: Eder
authors: Friederike
authors: F
authors: Cuello
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism*; D006333:Heart Failure / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D011493:Protein Kinase C / Q000378:metabolism*
chemical_list: C089212:protein kinase D; D011493:Protein Kinase C; D054769:G-Protein-Coupled Receptor Kinase 2; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases