Document Detail


Vascular smooth muscle cell proliferation requires both p38 and BMK1 MAP kinases.
MedLine Citation:
PMID:  12054430     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vascular smooth muscle cell (VSMC) proliferation is a key event in the progression of atherosclerosis. Induction of both c-fos (through the transcription factor Elk-1) and c-jun, both immediate early genes, is important for the stimulation of VSMC proliferation and migration. It was earlier found that p38 mitogen-activated protein (MAP) kinase upregulates c-jun gene transcription through phosphorylation of two myocyte enhancer factor 2 (MEF2) family transcription factors, MEF2A and MEF2C, while big MAP kinase 1 (BMK1) may upregulate c-jun gene transcription through MEF2A, MEF2C, and also MEF2D. Here, we report that inhibition of BMK1 by a dominant negative form of MEK5 or pharmacologic inhibition of p38 by SB 203580 additively suppress serum-induced VSMC proliferation. This additive effect of p38 and BMK1 inhibition implies that these two kinases coordinately regulate MEF2 transcription factors. The exclusive activation of MEF2D by BMK1 appears required for this cooperative upregulation of c-jun in VSMC, and coactivation of p38 and BMK1 also has additive effects on the activation of a reporter gene linked to the c-jun promoter in our experimental system. Thus, coordinate activity of both the p38 and BMK1 pathways appears necessary for optimal transcription of c-jun and, pari pasu, VSMC proliferation. These results may have implications for the future design of pharmacologic agents for inhibition of VSMC growth.
Authors:
Ming Zhao; Yawei Liu; Mingmin Bao; Yutaka Kato; Jiahuai Han; John W Eaton
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  400     ISSN:  0003-9861     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-06-10     Completed Date:  2002-06-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  199-207     Citation Subset:  IM    
Affiliation:
Division of Pathology II, Faculty of Health Sciences, Linköping University, Linköping SE-581 85, Sweden. ming.zhao@inr.liu.se
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MeSH Terms
Descriptor/Qualifier:
Animals
Arteriosclerosis / metabolism
Blood Proteins / pharmacology
Cell Division / drug effects,  physiology
Cell Line
Cells, Cultured
DNA-Binding Proteins / metabolism
Enzyme Activation / physiology
Epithelial Cells / cytology,  drug effects,  enzymology
Gene Expression / drug effects
Humans
JNK Mitogen-Activated Protein Kinases
MADS Domain Proteins
Male
Mitogen-Activated Protein Kinase 7
Mitogen-Activated Protein Kinases / genetics,  metabolism*
Muscle, Smooth, Vascular / cytology,  drug effects,  enzymology*
Myogenic Regulatory Factors
Promoter Regions, Genetic / physiology
Rats
Signal Transduction / physiology
Transcription Factors / metabolism
Transcription, Genetic / physiology
Up-Regulation / drug effects,  physiology
p38 Mitogen-Activated Protein Kinases
Grant Support
ID/Acronym/Agency:
R01 AI41637/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Blood Proteins; 0/DNA-Binding Proteins; 0/MADS Domain Proteins; 0/MEF2A protein, human; 0/MEF2C protein, human; 0/MEF2D protein, human; 0/Myogenic Regulatory Factors; 0/Transcription Factors; 0/myocyte-specific enhancer-binding factor 2; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 7; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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