The ShcA phosphotyrosine docking protein sensitizes cardiovascular signaling in the mouse embryo

Abstract

The ShcA gene products have served as a model for the analysis of phosphotyrosine-recognition domains, and for the functions of docking proteins during tyrosine kinase signaling. Here we show that ShcA is primarily expressed in the cardiovascular system during early mouse embryogenesis and regulates both heart development and establishment of mature blood vessels. Targeted mutation suggests that the ShcA adaptor is a pivotal target of tyrosine kinases that selectively potentiates activation of the MAP kinase pathway in the remodeling vasculature. Biochemical analysis of mutant cells shows that ShcA sensitizes cells to growth factor-induced MAP kinase activation, and also organizes cytoskeletal rearrangement in response to the extracellular matrix. ShcA may therefore orchestrate complex interactions within the vascular compartment by rendering cells permissive to respond to soluble and adhesive external cues.