The MAPK ERK1 is a negative regulator of the adult steady-state splenic erythropoiesis.
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.
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (CNRS; Unité Mixte de Recherche [UMR] 8104), 75014 Paris, France.
Soizic
S
Guihard
Denis
D
Clay
Laurence
L
Cocault
Nathalie
N
Saulnier
Paule
P
Opolon
Michèle
M
Souyri
Gilles
G
Pagès
Jacques
J
Pouysségur
Françoise
F
Porteu
Murielle
M
Gaudry
D000740:Anemia / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000502:physiology*; D004920:Erythropoiesis / Q000502:physiology*; D004921:Erythropoietin / Q000378:metabolism; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D016877:Oxidants / Q000633:toxicity; D010659:Phenylhydrazines / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000378:metabolism*
D055415:Bone Morphogenetic Protein 4; D016877:Oxidants; D010659:Phenylhydrazines; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; C030299:phenylhydrazine; D004921:Erythropoietin; D048052:Mitogen-Activated Protein Kinase 3