Document Detail


Activated MEK stimulates expression of AP-1 components independently of phosphatidylinositol 3-kinase (PI3-kinase) but requires a PI3-kinase signal To stimulate DNA synthesis.
MedLine Citation:
PMID:  9858556     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To investigate the contribution that ERK/mitogen-activated protein kinase signalling makes to cell cycle progression and gene expression, we have constructed cell lines to express an inducible version of activated MEK1. Using these cells, we show that activation of MEK leads to the expression of Fra-1 and Fra-2 but not c-Fos. Treatment of Ras-transformed cells with the MEK inhibitor PD098059 blocks expression of Fra-1 and Fra-2, showing that in Ras transformation ERK signalling is responsible for Fra-1 and Fra-2 expression. Activation of MEK1 in growth-arrested cells leads to DNA synthesis; however, ERK activation alone is insufficient because the induction of DNA synthesis is blocked by inhibition of phosphatidylinositol 3-kinase (PI3-kinase). Activation of PI3-kinase is indirect, perhaps through autocrine growth factors, and is required for the induction of cyclin D1.
Authors:
I Treinies; H F Paterson; S Hooper; R Wilson; C J Marshall
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  19     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-02-10     Completed Date:  1999-02-10     Revised Date:  2013-04-17    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  321-9     Citation Subset:  IM    
Affiliation:
CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratory, Institute of Cancer Research, London, SW3 6JB, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Animals
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
DNA / biosynthesis
Enzyme Activation
Gene Expression
MAP Kinase Kinase 1
Mice
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases*
Phosphatidylinositol 3-Kinases / metabolism*
Protein-Serine-Threonine Kinases / genetics,  metabolism*
Protein-Tyrosine Kinases / genetics,  metabolism*
Rabbits
Signal Transduction*
Transcription Factor AP-1 / metabolism*
Chemical
Reg. No./Substance:
0/Transcription Factor AP-1; 9007-49-2/DNA; EC 2.7.1.-/Map2k1 protein, mouse; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.12.2/MAP Kinase Kinase 1; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases
Comments/Corrections

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