Pulling back the curtain: The hidden functions of receptor tyrosine kinases in development.

Abstract

Receptor tyrosine kinases (RTKs) are a conserved superfamily of transmembrane growth factor receptors that drive numerous cellular processes during development and in the adult. Upon activation, multiple adaptors and signaling effector proteins are recruited to binding site motifs located within the intracellular domain of the RTK. These RTK-effector interactions drive subsequent intracellular signaling cascades involved in canonical RTK signaling. Genetic dissection has revealed that alleles of Fibroblast Growth Factor receptors (FGFRs) that lack all canonical RTK signaling still retain some kinase-dependent biological activity. Here we examine how genetic analysis can be used to understand the mechanism by which RTKs drive multiple developmental processes via canonical signaling while revealing noncanonical activities. Recent data from both FGFRs and other RTKs highlight potential noncanonical roles in cell adhesion and nuclear signaling. The data supporting such functions are discussed as are recent technologies that have the potential to provide valuable insight into the developmental significance of these noncanonical activities.