ERK1/2 activation in heart is controlled by melusin, focal adhesion kinase and the scaffold protein IQGAP1.

Abstract

Extracellular signal-regulated kinase 1/2 (ERK1/2) signalling is a key pathway in cardiomyocyte hypertrophy and survival in response to many different stress stimuli. We have previously characterized melusin as a muscle-specific chaperone protein capable of ERK1/2 signalling activation in the heart. Here, we show that in the heart, melusin forms a supramolecular complex with the proto-oncogene c-Raf, MEK1/2 (also known as MAPKK1/2) and ERK1/2 and that melusin-bound mitogen-activated protein kinases (MAPKs) are activated by pressure overload. Moreover, we demonstrate that both focal adhesion kinase (FAK) and IQ motif-containing GTPase activating protein 1 (IQGAP1), a scaffold protein for the ERK1/2 signalling cascade, are part of the melusin complex and are required for ERK1/2 activation in response to pressure overload. Finally, analysis of isolated neonatal cardiomyocytes indicates that both FAK and IQGAP1 regulate melusin-dependent cardiomyocyte hypertrophy and survival through ERK1/2 activation.

• Authors: Mauro Sbroggiò, Alessandro Bertero, Silvia Velasco, Federica Fusella, Emanuele De Blasio, Wadie F Bahou, Lorenzo Silengo, Emilia Turco, Mara Brancaccio, Guido Tarone
• Journal: Journal of cell science (J Cell Sci) Vol. 124 Issue Pt 20 Pg. 3515-24 (Oct 15 2011) ISSN: 1477-9137 [Electronic] England
• PMID: 22010199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytoskeletal Proteins
• Enzyme Inhibitors
• IQ motif containing GTPase activating protein 1
• Itgb1bp2 protein, mouse
• Molecular Chaperones
• Multienzyme Complexes
• Muscle Proteins
• ras GTPase-Activating Proteins
• Focal Adhesion Protein-Tyrosine Kinases
• Extracellular Signal-Regulated MAP Kinases

Topics

• Allosteric Regulation
• Animals
• Cardiomyopathy, Hypertrophic (drug therapy, metabolism, pathology, physiopathology)
• Cell Survival (drug effects)
• Cells, Cultured
• Cytoskeletal Proteins (genetics, metabolism)
• Enzyme Activation (drug effects, genetics)
• Enzyme Inhibitors (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Focal Adhesion Protein-Tyrosine Kinases (metabolism)
• Heart (drug effects, physiology, physiopathology)
• MAP Kinase Signaling System (drug effects, genetics)
• Mice
• Mice, Knockout
• Mice, Transgenic
• Molecular Chaperones (genetics, metabolism)
• Multienzyme Complexes (metabolism)
• Muscle Proteins (genetics, metabolism)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Stress, Physiological
• ras GTPase-Activating Proteins (genetics, metabolism)