Molecular mechanism of cofilin dephosphorylation by ouabain

Jaehoon Jung, Moonhee Kim, Suenghee Choi, Min Jeong Kim, Jae kyung Suh, Eung Chil Choi, Kyunglim Lee

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16 Scopus citations


We previously reported that phosphorylated cofilin-triosephosphate isomerase (TPI) complex interacts with Na,K-ATPase and enhances the pump activity through the phosphorylation of cofilin via Rho-mediated signaling pathway. In this study, we tested the hypothesis that the dephosphorylation of cofilin may be induced through Na,K-ATPase inhibition by ouabain. The phosphorylation level of cofilin by ouabain which decreases in a time- and dose-dependent manner in various human cell lines, remains unchanged by pretreatment with Src inhibitor, PP2; epidermal growth factor receptor (EGFR) inhibitor, AG1478; Raf-1 kinase (Raf) inhibitor, GW5074; and ERK kinase (MEK) inhibitor, PD98059, and by transfection of Ras dominant negative mutant (RasN17). This suggests that ouabain dephosphorylates cofilin through the Src/EGFR/Ras/Raf/MEK pathway. Ouabain activates Ras/Raf/MEK pathway, but down-regulates Rho kinase (ROCK)/LIM kinase (LIMK)/cofilin pathway, implying that there may be a cross-talk by ouabain between the Ras/Raf/MEK and the ROCK/LIMK/cofilin pathways. Immunofluorescence and flow cytometry suggest that ouabain-induced active form of cofilin may be involved in cytoskeletal reorganization and cell volume regulation. Thus, these findings demonstrate a new molecular mechanism for the dephosphorylation of cofilin through the inhibition of Na,K-ATPase by ouabain.

Original languageEnglish
Pages (from-to)2033-2040
Number of pages8
JournalCellular Signalling
Issue number11
StatePublished - Nov 2006

Bibliographical note

Funding Information:
This work was supported by a grant of the Molecular and Cellular BioDiscovery Research Program (M1-0311-00-0039) from Korean Ministry of Science and Technology, the Korean Health 21 R and D Project, Ministry of Health and Welfare (A050402), and the Korea Science and Engineering Foundation through CCSR at Ewha Womans University. Kim, M, Kim MJ, and Choi, S were supported by the Brain Korea 21 Project fellowship.


  • Cell volume
  • Cofilin dephosphorylation
  • Cytoskeleton
  • Na,K-ATPase
  • Ouabain


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