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

作者：Sbroggio Mauro; Bertero Alessandro; Velasco Silvia; Fusella Federica; De Blasio Emanuele; Bahou Wadie F; Silengo Lorenzo; Turco Emilia; Brancaccio Mara^*; Tarone Guido

来源：Journal of Cell Science, 2011, 124(20): 3515-3524.

DOI：10.1242/jcs.091140

• ERK1/2
• FAK
• IQGAP1
• Melusin
• Heart 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.

• 出版日期2011-10-15