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

  • Tamura K
  • Sudo T
  • Senftleben U
 et al. 
  • 30

    Readers

    Mendeley users who have this article in their library.
  • N/A

    Citations

    Citations of this article.

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.

Author-supplied keywords

  • Anemia/enzymology
  • Animal
  • Erythropoiesis/*physiology
  • Erythropoietin/genetics
  • Female
  • Fetal Development
  • Gamma Rays
  • Gene Expression
  • Gene Targeting/methods
  • Gestational Age
  • Hematopoietic Stem Cells
  • Human
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases/genetics/metabol
  • Stress
  • Support, Non-U.S. Gov't
  • Support, U.S. Gov't, Non-P.H.S.
  • Support, U.S. Gov't, P.H.S.
  • Tumor Cells, Cultured

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Authors

  • K Tamura

  • T Sudo

  • U Senftleben

  • A M Dadak

  • R Johnson

  • M Karin

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free