ErbB signaling in cardiac development and disease

Abstract

The ErbB family of receptor tyrosine kinases (RTKs) is a family of receptors that allow cells to interact with the extracellular environment and transduce signals to the nucleus that promote differentiation, migration and proliferation necessary for proper heart morphogenesis and function. This review focuses on the role of the ErbB family of receptor tyrosine kinases, and their importance in proper heart morphogenesis, as well as their role in maintenance and function of the adult heart. Studies from transgenic mouse models have shown the importance of ErbB receptors in heart development, and provide insight into potential future therapeutic targets to help reduce congenital heart defect (CHD) mortality rates and prevent disease in adults. Cancer therapeutics have also shed light to the ErbB receptors and signaling network, as undesired side effects have demonstrated their importance in adult cardiomyocytes and prevention of cardiomyopathies. This review will discuss ErbB receptor tyrosine kinases (RTK) in heart development and disease including valve formation and partitioning of a four-chambered heart as well as cardiotoxicity when ErbB signaling is attenuated in adults.

Figure 1. ErbB signaling in adult cardiomyocytes

Description: ErbB receptor signaling essential for cardiomyocyte function. Signal transduction is initiated upon ligand binding (red box), inducing dimerization and transphosphorylation of ErbB receptors. A simplified illustration of ErbB signaling is focused on signaling cascades relevant to cardiomyocyte function and survival, mediated by the Ras-MAPK, PI3K-AKT, Src-FAK, and Nkx2.5 pathways.[56]