The Role of PI3K/AKT and MAPK Signaling Pathways in Erythropoietin Signalization

Int J Mol Sci. 2021 Jul 19;22(14):7682. doi: 10.3390/ijms22147682.

Abstract

Erythropoietin (EPO) is a glycoprotein cytokine known for its pleiotropic effects on various types of cells and tissues. EPO and its receptor EPOR trigger signaling cascades JAK2/STAT5, MAPK, and PI3K/AKT that are interconnected and irreplaceable for cell survival. In this article, we describe the role of the MAPK and PI3K/AKT signaling pathways during red blood cell formation as well as in non-hematopoietic tissues and tumor cells. Although the central framework of these pathways is similar for most of cell types, there are some stage-specific, tissue, and cell-lineage differences. We summarize the current state of research in this field, highlight the novel members of EPO-induced PI3K and MAPK signaling, and in this respect also the differences between erythroid and non-erythroid cells.

Keywords: MAPK; PI3K; erythropoietin.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • Cell Survival / physiology
  • Erythropoiesis / physiology*
  • Erythropoietin / physiology*
  • Humans
  • MAP Kinase Signaling System
  • Models, Biological
  • Neoplasms / physiopathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Erythropoietin / physiology
  • Signal Transduction

Substances

  • Receptors, Erythropoietin
  • Erythropoietin
  • Proto-Oncogene Proteins c-akt