Document Detail

AP-1 regulates alpha2beta1 integrin expression by ERK-dependent signals during megakaryocytic differentiation of K562 cells.
MedLine Citation:
PMID:  15707584     Owner:  NLM     Status:  MEDLINE    
Mitogen-activated protein kinases (MAPKs) have been implicated as regulators of cellular differentiation. The biological effect of MAPK signaling in the nucleus is achieved by signal-responsive transcription factors. Here, we have investigated the connection of MAPKs, transcription factor AP-1, and alpha2beta1 integrin expression in K562 cells undergoing differentiation along the megakaryocytic pathway. We report that three distinct MAPKs, ERK, JNK, and p38, are activated during the TPA-induced megakaryocytic differentiation. Activation of MAPK pathways is followed by acquisition of the AP-1 DNA-binding and transactivation capacities. AP-1 DNA-binding activity consists primarily of JunD, c-Fos, and Fra-1, and is accompanied with the increased expression and phosphorylation of these subunits. While inhibition of JNK mainly prevents expression and phosphorylation of JunD and c-Jun, inhibition of the ERK pathway suppresses both phosphorylation and expression of Jun proteins, and expression of c-Fos and Fra-1. Furthermore, only the activity of the ERK pathway is essential for the differentiation response, as determined by expression of alpha2beta1 (CD49b) integrin. The importance of AP-1 as a mediator ERK signaling during differentiation is demonstrated by the findings that expression of c-fos siRNA and dominant negative AP-1/c-Jun(bZIP) downregulate the TPA- and ERK-induced expression of alpha2beta1 integrin mRNAs and proteins. Conversely, coexpression of JunD or c-Jun and c-Fos can induce alpha2beta1 integrin expression independently of upstream signals. Taken together, the results show that AP-1 is a nuclear target of the ERK-pathway and mediates alpha2beta1 integrin expression during megakaryocytic differentiation of K562 cells.
Minna Eriksson; Laura Arminen; Marja-Liisa Karjalainen-Lindsberg; Sirpa Leppä
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-11-18
Journal Detail:
Title:  Experimental cell research     Volume:  304     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-14     Completed Date:  2005-04-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  175-86     Citation Subset:  IM    
Molecular Cancer Biology Research Program, Biomedicum Helsinki and Haartman Institute, P.O. Box 63, FIN-00014 Helsinki, Finland.
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MeSH Terms
Cell Differentiation
Extracellular Signal-Regulated MAP Kinases / metabolism*
Integrin alpha2beta1 / metabolism*
JNK Mitogen-Activated Protein Kinases / metabolism
K562 Cells
MAP Kinase Signaling System
Megakaryocytes / cytology*,  metabolism
Proto-Oncogene Proteins c-fos / physiology
Repressor Proteins / physiology
Transcription Factor AP-1 / metabolism*
Reg. No./Substance:
0/Integrin alpha2beta1; 0/JDP2 protein, human; 0/Proto-Oncogene Proteins c-fos; 0/Repressor Proteins; 0/Transcription Factor AP-1; EC Signal-Regulated MAP Kinases; EC Mitogen-Activated Protein Kinases

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