Heart failure-specific changes in protein kinase signalling

TY - JOUR

T1 - Heart failure-specific changes in protein kinase signalling

AU - Lorenz, Kristina

AU - Stathopoulou, Konstantina

AU - Schmid, Evelyn

AU - Eder, Petra

AU - Cuello, Friederike

PY - 2014/6/1

Y1 - 2014/6/1

N2 - 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.

AB - 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.

KW - Animals

KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2

KW - Extracellular Signal-Regulated MAP Kinases

KW - G-Protein-Coupled Receptor Kinase 2

KW - Heart Failure

KW - Humans

KW - MAP Kinase Signaling System

KW - Protein Kinase C

U2 - 10.1007/s00424-014-1462-x

DO - 10.1007/s00424-014-1462-x

M3 - SCORING: Journal article

C2 - 24510065

VL - 466

SP - 1151

EP - 1162

JO - PFLUG ARCH EUR J PHY

JF - PFLUG ARCH EUR J PHY

SN - 0031-6768

IS - 6

ER -