mAKAP-A Master Scaffold for Cardiac Remodeling

Cardiac remodeling is regulated by an extensive intracellular signal transduction network. Each of the many signaling pathways in this network contributes uniquely to the control of cellular adaptation. In the last few years, it has become apparent that multimolecular signaling complexes or signalosomes are important for fidelity in intracellular signaling and for mediating crosstalk between the different signaling pathways. These complexes integrate upstream signals and control downstream effectors. In the cardiac myocyte, the protein mAKAP serves as a scaffold for a large signalosome that is responsive to cAMP, calcium, hypoxia, and mitogen-activated protein kinase signaling. The main function of mAKAP signalosomes is to modulate stress-related gene expression regulated by the transcription factors NFATc, MEF2, and HIF-1 and type II histone deacetylases that control pathological cardiac hypertrophy.