Focal adhesion kinase signaling in cardiac myocytes: new protein interactions and cell functions

Abstract

Heart diseases are frequently associated with mass increase (hypertrophy) and alterations of shape and dimension of cardiac chambers (remodeling) as an adaptive response to mechanic and neurohumoral stimuli. Hypertrophy mainly results from an increase of cardiomyocytes area, while remodeling is characterized by cell death and fibrosis, which are determinant factors for cardiac failure. Among the signaling mechanisms that regulate the hypertrophy as well as the survival of cardiomyocytes, the signaling mediated by focal adhesion kinase (FAK) has been emerged as a key target, however, the molecular mechanisms regulated by FAK remain poorly studied. The objectives of this proposal are to identify new interaction partners for FAK and show the involvement of this kinase in several pathways related to the myocytes survival. Preliminary results indicate that FAK may regulate potential interactors, including enzymes that act on survival through the DNA damage response, such as PARP1, DNA-PK1, MRE11A, and XRCC5. Such interactions will be investigated on cardiac myocytes H9C2 and on rat left ventricle by a combination of functional and structural sophisticated techniques. The identification of the new FAK interaction partners and cellular functions regulated by these kinase, which could impact on the development of heart failure, continues to be a challenge. (AU)