The Nck-interacting kinase phosphorylates ERM proteins for formation of lamellipodium by growth factors.

摘要: The mammalian Ste20-like Nck-interacting kinase (NIK) and its orthologs Misshapen in Drosophila Mig-15 Caenorhabditis elegans have a conserved function regulating cell morphology, although through poorly understood mechanisms. We report two previously unrecognized actions of NIK: regulation lamellipodium formation by growth factors phosphorylation the ERM proteins ezrin, radixin, moesin. regulate morphology plasma membrane dynamics reversibly anchoring actin filaments to integral proteins. In vitro assays show that NIK interacts directly with proteins, binding their N termini phosphorylating C-terminal threonine. cells, phosphorylated localize at distal margins lamellipodia, activity is necessary for induced EGF PDGF, but not thrombin. Lamellipodium extension response inhibited cells expressing kinase-inactive NIK, suppressed expression siRNA oligonucleotides, or ezrin T567A cannot be phosphorylated. These data suggest direct constitutes signaling mechanism controlling factor-induced protrusion morphology.