Erk1 and Erk2 are required for maintenance of hematopoietic stem cells and adult hematopoiesis

Blood. 2013 May 2;121(18):3594-8. doi: 10.1182/blood-2012-12-476200. Epub 2013 Feb 26.


Extracellular signal-regulated kinase 1 (Erk1) and Erk2 play crucial roles in cell survival, proliferation, cell adhesion, migration, and differentiation in many tissues. Here, we report that the absence of Erk1 and Erk2 in murine hematopoietic cells leads to bone marrow aplasia, leukopenia, anemia, and early lethality. Mice doubly-deficient in Erk1 and Erk2 show rapid attrition of hematopoietic stem cells and immature progenitors in a cell-autonomous manner. Reconstitution studies show that Erk1 and Erk2 play redundant and kinase-dependent functions in hematopoietic progenitor cells. Moreover, in cells transformed by the oncogenic KRas(G12D) allele, the presence of either Erk1 or Erk2 with intact kinase activity is sufficient to promote cytokine-independent proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / metabolism
  • Adult Stem Cells / physiology
  • Age Factors
  • Animals
  • Cell Proliferation
  • Cell Survival / genetics
  • Cells, Cultured
  • Hematopoiesis / genetics*
  • Hematopoietic Stem Cells / enzymology
  • Hematopoietic Stem Cells / physiology*
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / physiology*
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / physiology*


  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3