FES and FER: The F‑BAR Domain‑Containing Protein‑Tyrosine Kinases
Waheed Sangrar, Andrew W. Craig and Peter A. Greer
FES and FER are the only two members of a distinct subgroup of 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 recently solved F‑BAR domains of several Pombe CDC15 homology (PCH) adaptor proteins. PCH adaptor proteins bind phosphoinositides on curved membrane invaginations via their F‑BAR domains and recruit effectors of membrane‑cytoskeletal remodeling via their SH3 domains to promote receptor endocytosis. FES and FER signal from a diverse group of membrane receptors systems and have been implicated in regulating hematopoiesis and innate immunity. At the cellular level, FES and FER have been shown to regulate cadherin‑ and integrin‑mediated adhesion, receptor internalization, vesicular trafficking and cell migration. The recently recognized homology to F‑BAR domains in these kinases suggests a mechanistic basis for their localization at sites of dynamic membrane‑cytoskeletal remodeling. This chapter provides an overview of our current understanding of the structures of FES and FER PTKs, as well as evidence for their biochemical regulation and their cellular and physiological functions.