title: Function of Ahnak protein in aortic smooth muscle cell migration through Rac activation.
abstract: OBJECTIVE
  Ahnak protein acts as a scaffold protein networking phospholipase C-γ and protein kinase C-α, which subsequently stimulate an extracellular signal-regulated kinase (Erk) pathway. In mouse aortic smooth muscle cells (ASMCs), the activation of the signalling cascade ultimately promotes the cell migration through an unknown mechanism. We aimed to dissect the Ahnak-mediated cell signalling network involved in the migration of ASMCs.
  
  
  RESULTS
  Migration of ASMCs from wild-type mice was significantly increased by platelet-derived growth factor (PDGF) stimulation in transwell chamber and wound-healing assays, whereas migration of ASMCs from Ahnak knockout mice was reduced. Consistently, stimulation of wild-type ASMCs with PDGF resulted in Rac activation-mediated lamellipodial protrusion in migrating cells. In contrast, Ahnak knockout ASMCs displayed lower activation of Rac in response to PDGF and slow lamellipodial protrusion rate and cell migration. Ahnak signalling complex was analysed by immunoprecipitation with antibody to p21-activated protein kinase (PAK). Ahnak protein was shown to function as the signalling scaffold interacting with the multiple protein complex of Erk, PAK, and p21-activated kinase-interacting exchange factor β. The proposed role of Ahnak in cell migration was examined using a restenosis model in which the carotid arteries of mice were subjected to post-ligation injury. We show neointimal formation and SMC migration after ligation injury in Ahnak knockout mice were significantly retarded compared with wild-type mice.
  
  
  CONCLUSIONS
  Ahnak protein plays an important scaffolding function connecting Erk and Rac activation in PDGF-dependent migration of ASMC.
authors.affiliation: Department of Life Science,  Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul 120-750,  Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Lim
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Kang
authors.forename: Jung Mi
authors.initials: JM
authors.lastname: Lim
authors.forename: Dong Min
authors.initials: DM
authors.lastname: Kang
authors.forename: Je Kyung
authors.initials: JK
authors.lastname: Seong
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Kang
authors.forename: Yun Soo
authors.initials: YS
authors.lastname: Bae
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D058426:Neointima; D009363:Neoplasm Proteins / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011554:Pseudopodia / Q000502:physiology; D064067:Rho Guanine Nucleotide Exchange Factors; D054462:p21-Activated Kinases / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000502:physiology*
chemical_list: C489572:Ahnak protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor; D064067:Rho Guanine Nucleotide Exchange Factors; D054462:p21-Activated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020744:rac GTP-Binding Proteins