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Selected Publication:

Type of publication: Journal Article
Type of document: Full Paper

Year: 2000

Authors: Tamura, K; Sudo, T; Senftleben, U; Dadak, AM; Johnson, R; Karin, M

Title: Requirement for p38alpha in erythropoietin expression: a role for stress kinases in erythropoiesis.

Source: Cell. 2000; 102(2):221-231

Authors Vetmeduni Vienna:

Dadak Agnes

Vetmed Research Units
Institute of Pharmacology and Toxicology

Project(s): Activation and function of hypoxia inducible transcription factors

Activity of the p38alpha MAP kinase is stimulated by various stresses and hematopoietic growth factors. A role for p38alpha in mouse development and physiology was investigated by targeted disruption of the p38alpha locus. Whereas some p38alpha(-/-) embryos die between embryonic days 11.5 and 12.5, those that develop past this stage have normal morphology but are anemic owing to failed definitive erythropoiesis, caused by diminished erythropoietin (Epo) gene expression. As p38alpha-deficient hematopoietic stem cells reconstitute lethally irradiated hosts, p38alpha function is not required downstream of Epo receptor. Inhibition of p38 activity also interferes with stabilization of Epo mRNA in human hepatoma cells undergoing hypoxic stress. The p38alpha MAP kinase plays a critical role linking developmental and stress-induced erythropoiesis through regulation of Epo expression.

Keywords Pubmed: Anemia/enzymology
Embryonic and Fetal Development
Gamma Rays
Gene Expression
Gene Targeting/methods
Gestational Age
Hematopoietic Stem Cells
Mice, Inbred C57BL
Mice, Knockout
Mitogen-Activated Protein Kinases/genetics
Mitogen-Activated Protein Kinases/metabolism
Mitogen-Activated Protein Kinases/physiology*
Stress, Physiological
Tumor Cells, Cultured
p38 Mitogen-Activated Protein Kinases

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