Thrombopoietin (TPO) induces tyrosine phosphorylation and activation of STAT5 and STAT3

FEBS Lett. 1995 Aug 14;370(1-2):63-8. doi: 10.1016/0014-5793(95)00796-c.

Abstract

The growth and differentiation of megakaryocytes are regulated by thrombopoietin (TPO), a recently characterized cytokine which exerts its effects via a member of the hematopoietin receptor superfamily, c-Mpl. Since many cytokines which bind hematopoietin receptors activate the STAT family of transcription factors, we investigated whether STAT proteins were activated by TPO. TPO induced the formation of a DNA-binding complex recognizing a known STAT-binding sequence. STAT5 was a major component of this DNA-binding complex, and STAT5 was tyrosine phosphorylated in response to TPO. Additionally, TPO-induced the tyrosine phosphorylation and DNA-binding activity of STAT3. Together with the recent demonstration of JAK2 activation in response to TPO, the data presented here define a rapid signaling pathway likely to be important in TPO-induced gene regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cell Line
  • Cytokines / pharmacology*
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Enzyme Activation
  • Humans
  • Janus Kinase 2
  • Leukemia, Megakaryoblastic, Acute
  • Megakaryocytes / cytology
  • Megakaryocytes / drug effects
  • Megakaryocytes / metabolism
  • Milk Proteins*
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Phosphorylation
  • Phosphotyrosine
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins*
  • Recombinant Proteins / pharmacology
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor
  • Signal Transduction
  • Thrombopoietin / pharmacology*
  • Trans-Activators / metabolism*
  • Tumor Cells, Cultured
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Cytokines
  • DNA-Binding Proteins
  • Milk Proteins
  • Oligodeoxyribonucleotides
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • STAT5 Transcription Factor
  • Trans-Activators
  • Phosphotyrosine
  • Tyrosine
  • Thrombopoietin
  • Protein-Tyrosine Kinases
  • JAK2 protein, human
  • Janus Kinase 2