ABSTRACT
FES and FER are the only two members o f a distinct subgroup o f the protein-tyrosine kinase (PTK) family. What distinguishes them from other PTKs and indeed all other kinases, are their unique amino-terminal domains, which contain sequences homologous to the recendy solved F-BAR domains o f several Pombe C D C 15 homology (PCH) adaptor proteins. PCH adaptor proteins bind phosphoinositides on curved membrane invaginations via their F-BAR domains and recruit effectors o f membrane-cytoskeletal remodeling via their SH3 domains to promote receptor endocytosis. FES and FER signal from a diverse group o f membrane receptors systems and have been implicated in regulating hematopoiesis and innate immunity. At the cel lular level, FES and FER have been shown to regulate cadherin-and integrin-mediated adhesion, receptor internalization, vesicular trafficking and cell migration. The recently recognized homol ogy to F-BAR domains in these kinases suggests a mechanistic basis for their localization at sites o f dynamic membrane-cytoskeletal remodeling. This chapter provides an overview o f our current understanding o f the structures o f FES and FER PTKs, as well as evidence for their biochemical regulation and their cellular and physiological functions.
