title: Phosphorylation and reorganization of vimentin by p21-activated kinase (PAK).
abstract: BACKGROUND
  Intermediate filament (IF) is one of the three major cytoskeletal filaments. Vimentin is the most widely expressed IF protein component. The Rho family of small GTPases, such as Cdc42, Rac and Rho, are thought to control the organization of actin filaments as well as other cytoskeletal filaments.
  
  
  RESULTS
  We determined if the vimentin filaments can be regulated by p21-activated kinase (PAK), one of targets downstream of Cdc42 or Rac. In vitro analyses revealed that vimentin served as an excellent substrate for PAK. This phosphorylated vimentin lost the potential to form 10 nm filaments. We identified Ser25, Ser38, Ser50, Ser65 and Ser72 in the amino-terminal head domain as the major phosphorylation sites on vimentin for PAK. The ectopic expression of constitutively active PAK in COS-7 cells induced vimentin phosphorylation. Fibre bundles or granulates of vimentin were frequent in these transfected cells. However, the kinase-inactive mutant induced neither vimentin phosphorylation nor filament reorganization.
  
  
  CONCLUSIONS
  Our observations suggest that PAK may regulate the reorganization of vimentin filaments through direct vimentin phosphorylation.
authors.affiliation: Division of Biochemistry, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464-8681, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Goto
authors.forename: Kazushi
authors.initials: K
authors.lastname: Tanabe
authors.forename: Edward
authors.initials: E
authors.lastname: Manser
authors.forename: Louis
authors.initials: L
authors.lastname: Lim
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yasui
authors.forename: Masaki
authors.initials: M
authors.lastname: Inagaki
mesh_terms: D000818:Animals; D019556:COS Cells; D007382:Intermediate Filaments / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014746:Vimentin / Q000737:chemistry / Q000378:metabolism*; D054462:p21-Activated Kinases
chemical_list: D011994:Recombinant Proteins; D014746:Vimentin; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases