Ablation of p21-activated kinase-1 in mice promotes isoproterenol-induced cardiac hypertrophy in association with activation of Erk1/2 and inhibition of protein phosphatase 2A

• Published in: Journal of molecular and cellular cardiology Vol. 51; no. 6; pp. 988 - 996
• Main Authors: Taglieri, Domenico M, Monasky, Michelle M, Knezevic, Ivana, Sheehan, Katherine A, Lei, Ming, Wang, Xin, Chernoff, Jonathan, Wolska, Beata M, Ke, Yunbo, Solaro, R. John
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2011
• Subjects: Animals; Calcium - metabolism; Cardiomegaly - chemically induced; Cardiomegaly - enzymology; Cardiomegaly - genetics; Cardiomegaly - pathology; Cardiovascular; Disease Models, Animal; Echocardiography; Enzyme Activation - drug effects; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Gene Knockout Techniques; Isoproterenol - administration & dosage; Isoproterenol - adverse effects; Isoproterenol - pharmacology; Male; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 3 - metabolism; Mitogen-activated protein kinases; Myocardial hypertrophy; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myofibrils - metabolism; p21-Activated Kinases - deficiency; p21-Activated Kinases - genetics; p38 MAPK; Pak-1; Phosphorylation - drug effects; Protein Kinase Inhibitors - pharmacology; Protein Phosphatase 2 - antagonists & inhibitors; Pyrazoles - pharmacology; Pyridazines - pharmacology; Signal Transduction; Troponin I; cTnI; cardiac troponin T; extracellular signal-regulated kinase; LVPWD; constitutively active; JNK; myosin binding protein C; LV; Pak-1; left ventricular diastolic anterior wall thickness; cardiac troponin I; Lac operon Z; tropomyosin; EDT; EDV; cTnT; Tm; MyBPC; Jun N-terminal Kinase; Mitogen-activated protein kinases; P38 mitogen-activated protein kinase; Western immunoblotting; 2-D DIGE; 2-D Difference In Gel Electrophoresis; P38 MAPK; MAPK; Troponin I; wild type; lacZ; Erk; heterozygous; isoproterenol; WB; left ventricular/ventricle; FS; P21-activated kinase; mitogen-activated protein kinase; LVAWD; protein phosphatase 2A; end-diastolic volume; left ventricular diastolic posterior wall thickness; WT; CA; knockout; ISO; KO; Myocardial hypertrophy; ESV; end-systolic volume; friend Virus B-Type; control; PP2A; transmitral early filling deceleration time; FVB; CTRL; HE; fractional shortening

Abstract Earlier investigations in our lab indicated an anti-adrenergic effect induced by activation of p21-activated kinase (Pak-1) and protein phosphatase 2A (PP2A). Our objective was to test the hypothesis that Pak-1/PP2A is a signaling cascade controlling stress-induced cardiac growth. We determ...