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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents



ID: 313282.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
MEK hyperphosphorylation coincides with cell cycle shut down of cultured smooth muscle cells
Authors:Vogel, S.; Kubin, T.; von der Ahe, D.; Deindl, E.; Schaper, W.; Zimmermann, R.
Date of Publication (YYYY-MM-DD):2006-05-26
Title of Journal:J Cell Physiol
Journal Abbrev.:J Cell Physiol
Volume:246
Start Page:25
End Page:34
Audience:Not Specified
Abstract / Description:Smooth muscle cells (SMCs) form the backbone of arteries and their proliferation hallmarks collateral vessel growth, a process termed arteriogenesis, as well as pathogenic responses such as restenosis. Since signaling pathways in SMCs are the main targets for therapeutic interventions, we aimed to determine how and to what extent the activation of the ubiquitous MEK-ERK signaling pathway correlates with important in vivo phenomena such as dedifferentiation, nuclear activation and proliferation of SMCs. Specificity of this pathway was monitored using MEK inhibitors UO126 and PD98059 in platelet derived growth factor-AB (PDGF-AB)- and fibroblast growth factor-2 (FGF-2)-stimulated SMCs. PDGF-AB induced a rapid MEK activation followed by phosphorylation of the MEK substrates ERK1/2 while FGF-2 showed a less pronounced and delayed activation. Both growth factors triggered a marked phosphorylation of c-Myc and expression of Egr1. Pretreatment with MEK inhibitors suppressed the activation of the ERK cascade, abolished the down-regulation of desmin and led to cell cycle arrest. However, the reversibility of p27(Kip1) down-regulation by UO126 was mainly observed after PDGF-AB stimulation, indicating MEK independent p27(Kip1) down-regulation by FGF-2. Surprisingly, treatment of SMCs with UO126 or PD98059 increased the level of MEK phosphorylation in a dose dependent manner at serine residues 217/221 in the presence as well as in the absence of both growth factors. Our results strongly imply that depending on the environmental context phosphorylation of serines 217/221 serves as an "on" as well as an "off " switch. (c) 2005 Wiley-Liss, Inc.
Free Keywords:Smooth muscle cells MEK Hyperphosphorylation Cell culture
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=...
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