Document Detail

Repression of Stat3 activity by activation of mitogen-activated protein kinase (MAPK).
MedLine Citation:
PMID:  9872331     Owner:  NLM     Status:  MEDLINE    
STAT proteins are activated by phosphorylation at specific tyrosine residue at the carboxy-terminus which is required for dimer-formation, nuclear translocation, DNA binding and transcriptional activity in cells treated with cytokines and growth factors. Recent studies have indicated that STATs are also phosphorylated by MAPK, or extracellular signal-regulated kinase (ERK) on serine. We investigated the role of ERK on the regulation of STAT activity. Here, we report that ERK2 activated by its upstream kinase, MEK1, represses Stat3 transcriptional activity induced by Src or Jak-2. To unravel the mechanism of repression, we further showed that Stat3 DNA binding activity and its tyrosine phosphorylation are also inhibited under the same conditions. ERK2 phosphorylates Stat3 on three serine-containing peptides and decreases its tyrosine phosphorylation induced by EGF treatment. We also detected an association of ERK2 and Stat3 in vivo which is modulated positively by activation of ERK2, but negatively by Jak2. We propose that MAP kinase cascade may negatively regulate Stat3 activities by decreasing its tyrosine phosphorylation and also possibly by association.
N Jain; T Zhang; S L Fong; C P Lim; X Cao
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  17     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1998 Dec 
Date Detail:
Created Date:  1999-01-26     Completed Date:  1999-01-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  3157-67     Citation Subset:  IM    
Signal Transduction Laboratory, Institute of Molecular and Cell Biology, National University of Singapore.
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MeSH Terms
3T3 Cells
COS Cells
Calcium-Calmodulin-Dependent Protein Kinases / genetics,  metabolism*
Cell Line, Transformed
DNA-Binding Proteins / genetics,  metabolism*
Enzyme Activation
Gene Expression Regulation
Mitogen-Activated Protein Kinase 1
Oncogene Protein pp60(v-src) / genetics,  metabolism
STAT3 Transcription Factor
Trans-Activators / genetics,  metabolism*
Transcription, Genetic
Reg. No./Substance:
0/DNA-Binding Proteins; 0/STAT3 Transcription Factor; 0/Stat3 protein, mouse; 0/Stat3 protein, rat; 0/Trans-Activators; 55520-40-6/Tyrosine; EC Protein pp60(v-src); EC Protein Kinases; EC Protein Kinase 1

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