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PMID: 15121870 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Extracellular signal-regulated kinase induces the megakaryocyte GPIIb/CD41 gene through MafB/Kreisler.

Molecular and cellular biology ·Vol. 24 ·No. 10 ·2004-05-00 ·Pages 4534-45

Sevinsky JR, Whalen AM, Ahn NG

Abstract

Extracellular signal-regulated kinase (ERK) facilitates cell cycle progression in most mammalian cells, but in certain cell types prolonged signaling through this pathway promotes differentiation and lineage-specific gene expression through mechanisms that are poorly understood. Here, we characterize the transcriptional regulation of platelet GPIIb integrin (CD41) by ERK during megakaryocyte differentiation. ERK-dependent transactivation involves the proximal promoter of GPIIb within 114 bp upstream of the transcriptional start site. GATA, Ets, and Sp1 consensus sequences within this region are each necessary and function combinatorially in ERK-activated transcription. MafB/Kreisler is induced in response to ERK and synergizes with GATA and Ets to enhance transcription from the proximal promoter. The requirement for MafB in promoter regulation is demonstrated by inhibition of transactivation following dominant-negative or antisense suppression of MafB function. Thus, ERK promotes megakaryocyte differentiation by coordinate regulation of nuclear factors that synergize in GPIIb promoter regulation. These results establish a novel role for MafB as a regulator of ERK-induced gene expression.

MeSH Terms
Avian Proteins Base Sequence DNA/genetics DNA-Binding Proteins/genetics,metabolism Erythroid-Specific DNA-Binding Factors Gene Expression Regulation Humans K562 Cells MafB Transcription Factor Megakaryocytes/immunology,metabolism Mitogen-Activated Protein Kinases/genetics,metabolism Oncogene Proteins/genetics,metabolism Platelet Membrane Glycoprotein IIb/genetics,metabolism Promoter Regions, Genetic Proto-Oncogene Proteins/genetics,metabolism Proto-Oncogene Proteins c-ets Recombinant Proteins/genetics,metabolism Trans-Activators/genetics,metabolism Transcription Factors/genetics,metabolism Transfection
Chemicals
Avian Proteins DNA-Binding Proteins Erythroid-Specific DNA-Binding Factors MAFB protein, human MafB Transcription Factor Oncogene Proteins Platelet Membrane Glycoprotein IIb Proto-Oncogene Proteins Proto-Oncogene Proteins c-ets Recombinant Proteins Trans-Activators Transcription Factors DNA Mitogen-Activated Protein Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sevinsky Joel R
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
Whalen Anne M
Ahn Natalie G
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.10.4534-4545.2004
Published
2004-05-00
Pages
4534-45
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC400447
Subset
IM
Grants
NIGMS NIH HHS · T32 GM007135 · United States
NCI NIH HHS · R01-CA79801 · United States
NIGMS NIH HHS · T32-GM07135 · United States
External Links
PubMed source DOI: 10.1128/MCB.24.10.4534-4545.2004 PMC Full Text View journal details
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