Inhibition of erythropoietin-induced mitogenesis by a kinase-deficient form of Jak2.

Academic Article

Abstract

  • Receptors for a variety of hematopoietins, interferons alpha/beta and gamma, and growth hormone have recently been shown to mediate rapid, ligand-dependent activation of the Janus-type cytosolic protein-tyrosine kinases Jak1, Jak2, and/or tyk-2. This finding extends relatedness among class I and II cytokine receptors to a functional context and provides an initially satisfying mechanistic analogy to protein-tyrosine kinase-encoding receptors of the epidermal growth factor/platelet-derived growth factor/insulin family. Through the construction and expression of a kinase-deficient form of Jak2 (JK2 delta VIII) in interleukin-3 (IL-3)/erythropoietin (Epo)-dependent DAER cells, we have tested whether activation of Jak2 is required for induced mitogenesis via these class I cytokine receptors. Ectopic expression of JK2 delta VIII inhibited Epo- and IL-3-induced activation of endogenous wild-type Jak2, transiently attenuated IL-3-dependent growth, and essentially abrogated Epo-induced proliferation in this model system. These dominant-negative effects provide the first direct experimental evidence for an essential role for Janus kinase activation in mitogenesis and suggest that distinct effectors may mediate IL-3-induced versus Epo-induced pathways.
  • Authors

  • Zhuang, H
  • Patel, SV
  • He, TC
  • Sonsteby, SK
  • Niu, Z
  • Wojchowski, Don
  • Status

    Publication Date

  • August 26, 1994
  • Published In

    Keywords

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Division
  • Cells, Cultured
  • DNA Mutational Analysis
  • Erythropoietin
  • Interleukin-3
  • Janus Kinase 2
  • Mitogens
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Receptors, Interleukin-3
  • Signal Transduction
  • Pubmed Id

  • 8063772
  • Start Page

  • 21411
  • End Page

  • 21414
  • Volume

  • 269
  • Issue

  • 34