University of Veterinary Medicine Vienna - Research portal

Diagrammed Link to Homepage University of Veterinary Medicine, Vienna

Selected Publication:

Publication type: Journal Article
Document type: Full Paper

Year: 2000

Author(s): 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


Abstract:
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
Animals
Embryonic and Fetal Development
Erythropoiesis/physiology*
Erythropoietin/genetics
Female
Gamma Rays
Gene Expression
Gene Targeting/methods
Gestational Age
Hematopoietic Stem Cells
Humans
Male
Mice
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


© University of Veterinary Medicine ViennaHelp and Downloads