Focal Adhesion: Eph Kinases Suppress the FAKs.

Abstract

Eph kinases and their cognate ligands, ephrins, are located at the surface of cells in reciprocal compartments of embryos where they define organ boundaries by restricting cell migration. Though it remains unknown how Eph kinases and ephrins delineate these boundaries, it is likely that intracellular cell adhesion proteins are substrates for Eph kinases. Miao et al. demonstrate that the transmembrane receptor kinase EphA2 associates in a ligand-independent manner with focal adhesion kinase (FAK). Activation of EphA2 resulted in recruitment of the protein tyrosine phosphatase SHP-2, which dephosphorylates and inactivates FAK. Paxillin, a cytoskeletal substrate of FAK, also became less phosphorylated as a result of EphA2 activation, though, it is unclear whether this is from direct action of SHP-2 or inactivated FAK. Miao et al. also show that the SHP-2-dependent deactivation of FAK precedes the dissociation of FAK from the EphA2 receptor, cell rounding, and presumed focal adhesion disassembly. Thus, Eph kinase activation through cell-cell contact could generate a negative signal that inhibits cell spreading and migration.Miao, H., Burnett, E., Kinch, M., Simon, E., and Wang, B. (2000) Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nat. Cell Biol. 2: 62-69. [Online Journal]