title: IGF-I promotes Schwann cell motility and survival via activation of Akt.
abstract: We previously reported insulin-like growth factor-I (IGF-I) promotes Schwann cell (SC) motility and rescues SC from apoptosis induced by serum deprivation. This effect is mediated by phosphatidylinositol-3 (PI-3) kinase. In the current study, we examined the role of Akt, a downstream kinase of PI-3K, in SC motility and IGF-I mediated protection from apoptosis. IGF-I induces Akt phosphorylation at Ser473, an event which may be blocked by pretreatment with a PI-3K inhibitor, LY294002. In dominant negative K179M Akt (K179M) transfected SC, however, Akt is not activated in response to IGF-I. In addition, IGF-I is unable to promote SC motility and survival in K179M SC. These results suggest a critical role for Akt in IGF-I mediated motility and survival in SC.
authors.affiliation: Department of Neurology, University of Michigan, 200 Zina Pitcher Place, 4414 Kresge III, Ann Arbor, MI 48109-0588, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Cheng
authors.forename: M
authors.initials: M
authors.lastname: Steinway
authors.forename: C L
authors.initials: CL
authors.lastname: Delaney
authors.forename: T F
authors.initials: TF
authors.lastname: Franke
authors.forename: E L
authors.initials: EL
authors.lastname: Feldman
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D020125:Mutation, Missense; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects; D014162:Transfection
chemical_list: D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494918:AKT1 protein, human; C494920:Akt1 protein, rat