Document Detail

The MAPK ERK1 is a negative regulator of the adult steady-state splenic erythropoiesis.
MedLine Citation:
PMID:  20223923     Owner:  NLM     Status:  MEDLINE    
The mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase 1 (ERK1) and ERK2 are among the main signal transduction molecules, but little is known about their isoform-specific functions in vivo. We have examined the role of ERK1 in adult hematopoiesis with ERK1(-/-) mice. Loss of ERK1 resulted in an enhanced splenic erythropoiesis, characterized by an accumulation of erythroid progenitors in the spleen, without any effect on the other lineages or on bone marrow erythropoiesis. This result suggests that the ablation of ERK1 induces a splenic stress erythropoiesis phenotype. However, the mice display no anemia. Deletion of ERK1 did not affect erythropoietin (EPO) serum levels or EPO/EPO receptor signaling and was not compensated by ERK2. Splenic stress erythropoiesis response has been shown to require bone morphogenetic protein 4 (BMP4)-dependent signaling in vivo and to rely on the expansion of a resident specialized population of erythroid progenitors, termed stress erythroid burst-forming units (BFU-Es). A great expansion of stress BFU-Es and increased levels of BMP4 mRNA were found in ERK1(-/-) spleens. The ERK1(-/-) phenotype can be transferred by bone marrow cells. These findings show that ERK1 controls a BMP4-dependent step, regulating the steady state of splenic erythropoiesis.
Soizic Guihard; Denis Clay; Laurence Cocault; Nathalie Saulnier; Paule Opolon; Mich?le Souyri; Gilles Pag?s; Jacques Pouyss?gur; Fran?oise Porteu; Murielle Gaudry
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-11
Journal Detail:
Title:  Blood     Volume:  115     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-07     Completed Date:  2010-05-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3686-94     Citation Subset:  AIM; IM    
Institut Cochin, Universit? Paris Descartes, Centre National de la Recherche Scientifique (CNRS; Unit? Mixte de Recherche [UMR] 8104), 75014 Paris, France.
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MeSH Terms
Anemia / chemically induced,  pathology*
Blotting, Western
Bone Marrow Transplantation
Bone Morphogenetic Protein 4 / genetics,  metabolism
Colony-Forming Units Assay
Erythroid Precursor Cells / cytology,  physiology*
Erythropoiesis / physiology*
Erythropoietin / metabolism
Flow Cytometry
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 3 / physiology*
Oxidants / toxicity
Phenylhydrazines / toxicity
RNA, Messenger / genetics,  metabolism
Receptors, Erythropoietin / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Spleen / cytology,  metabolism*
Reg. No./Substance:
0/Bone Morphogenetic Protein 4; 0/Oxidants; 0/Phenylhydrazines; 0/RNA, Messenger; 0/Receptors, Erythropoietin; 100-63-0/phenylhydrazine; 11096-26-7/Erythropoietin; EC Protein Kinase 3

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