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Function of Ahnak protein in aortic smooth muscle cell migration through Rac activation

Title
Function of Ahnak protein in aortic smooth muscle cell migration through Rac activation
Authors
Lim H.J.Kang D.H.Lim J.M.Kang D.M.Seong J.K.Kang S.W.Bae Y.S.
Ewha Authors
배윤수강상원강동민강동훈
SCOPUS Author ID
배윤수scopus; 강상원scopus; 강동민scopus; 강동훈scopus
Issue Date
2013
Journal Title
Cardiovascular Research
ISSN
0008-6363JCR Link
Citation
vol. 97, no. 2, pp. 302 - 310
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
AimsAhnak 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.Methods and resultsMigration 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.ConclusionAhnak protein plays an important scaffolding function connecting Erk and Rac activation in PDGF-dependent migration of ASMC. © 2013 The Author.
DOI
10.1093/cvr/cvs311
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자연과학대학 > 생명과학전공 > Journal papers
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