Open AccessERK1/2 activation in heart is controlled by melusin, focal adhesion kinase and the scaffold protein IQGAP1
Author(s) -
Mauro Sbroggiò,
Alessandro Bertero,
Silvia Velasco,
Federica Fusella,
Emanuele De Blasio,
Wadie F. Bahou,
Lorenzo Silengo,
Emilia Turco,
Mara Brancaccio,
Guido Tarone
Publication year - 2011
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.091140
Subject(s) - iqgap1 , scaffold protein , microbiology and biotechnology , biology , pressure overload , kinase , focal adhesion , mapk/erk pathway , protein kinase a , small gtpase , signal transduction , muscle hypertrophy , endocrinology , cardiac hypertrophy
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.