title: Laminin-1 activates Cdc42 in the mechanism of laminin-1-mediated neurite outgrowth.
abstract: Here, we investigated the role of the small Rho GTPases Rac, Cdc42, and Rho in the mechanism of laminin-1-mediated neurite outgrowth in PC12 cells. PC12 cells were transfected with plasmids expressing wild-type and dominant-negative mutants of Rac (RacN17), Cdc42 (Cdc42N17), or Rho (RhoN19). Over 90% of the dominant-negative Rho- and Rac-transfected cells extended neurites when plated on laminin-1; however, none of the PC12 cells transfected with the dominant-negative Cdc42 mutant extended neurites. In cells cotransfected with plasmids expressing c-Jun N-terminal kinase and wild-type Cdc42, laminin-1 treatment stimulated detectable levels of c-Jun phosphorylation. Further, cotransfection with c-Jun N-terminal kinase and the dominant-negative Cdc42 mutant blocked laminin-1-mediated c-Jun phosphorylation. Transfection with either wild-type Rac or the dominant-negative Rac did not effect c-Jun phosphorylation. These data demonstrate that Cdc42 is activated by laminin-1 and that Cdc42 activation is required in the mechanism of laminin-1-mediated neurite outgrowth.
authors.affiliation: Department of Pharmacology, State University of New York at Stony Brook, Stony Brook, New York, 11794-8651, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Weston
authors.forename: L
authors.initials: L
authors.lastname: Anova
authors.forename: C
authors.initials: C
authors.lastname: Rialas
authors.forename: J M
authors.initials: JM
authors.lastname: Prives
authors.forename: B S
authors.initials: BS
authors.lastname: Weeks
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D007797:Laminin / Q000378:metabolism*; D016296:Mutagenesis; D016501:Neurites / Q000502:physiology*; D016716:PC12 Cells; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D007797:Laminin; D016755:Proto-Oncogene Proteins c-jun; C121346:laminin 1; D020764:cdc42 GTP-Binding Protein