title: Epidermal growth factor induction of front-rear polarity and migration in keratinocytes is mediated by integrin-linked kinase and ELMO2.
abstract: Epidermal growth factor (EGF) is a potent chemotactic and mitogenic factor for epidermal keratinocytes, and these properties are central for normal epidermal regeneration after injury. The involvement of mitogen-activated protein kinases as mediators of the proliferative effects of EGF is well established. However, the molecular mechanisms that mediate motogenic responses to this growth factor are not clearly understood. An obligatory step for forward cell migration is the development of front-rear polarity and formation of lamellipodia at the leading edge. We show that stimulation of epidermal keratinocytes with EGF, but not with other growth factors, induces development of front-rear polarity and directional migration through a pathway that requires integrin-linked kinase (ILK), Engulfment and Cell Motility-2 (ELMO2), integrin β1, and Rac1. Furthermore, EGF induction of front-rear polarity and chemotaxis require the tyrosine kinase activity of the EGF receptor and are mediated by complexes containing active RhoG, ELMO2, and ILK. Our findings reveal a novel link between EGF receptor stimulation, ILK-containing complexes, and activation of small Rho GTPases necessary for acquisition of front-rear polarity and forward movement.
authors.affiliation: Department of Physiology and Pharmacology, University of Western Ontario, London, ON N6A 5C1, Canada.
authors.forename: Ernest
authors.initials: E
authors.lastname: Ho
authors.forename: Lina
authors.initials: L
authors.lastname: Dagnino
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D019012:Integrin beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D004815:Epidermal Growth Factor; D019012:Integrin beta1; D017346:Protein Serine-Threonine Kinases; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D000099200:Scaffold Protein ILK; C544335:Elmo2 protein, mouse