ets-2 is a target for an akt (Protein kinase B)/jun N-terminal kinase signaling pathway in macrophages of motheaten-viable mutant mice

J L Smith, A E Schaffner, J K Hofmeister, M Hartman, G Wei, D Forsthoefel, D A Hume, M C Ostrowski

Research output: Contribution to journalArticlepeer-review

Abstract

The transcription factor ets-2 was phosphorylated at residue threonine 72 in a colony-stimulating factor 1 (CSF-1)- and mitogen-activated protein kinase-independent manner in macrophages isolated from motheaten-viable (me-v) mice. The CSF-1 and ets-2 target genes coding for Bcl-x, urokinase plasminogen activator, and scavenger receptor were also expressed at high levels independent of CSF-1 addition to me-v cells. Akt (protein kinase B) was constitutively active in me-v macrophages, and an Akt immunoprecipitate catalyzed phosphorylation of ets-2 at threonine 72. The p54 isoform of c-jun N-terminal kinase-stress-activated kinase (JNK- SAPK) coimmunoprecipitated with Akt from me-v macrophages, and treatment of me-v cells with the specific phosphatidylinositol 3-kinase inhibitor LY294002 decreased cell survival, Akt and JNK kinase activities, ets-2 phosphorylation, and Bcl-x mRNA expression. Therefore, ets-2 is a target for phosphatidylinositol 3-kinase-Akt-JNK action, and the JNK p54 isoform is an ets-2 kinase in macrophages. Constitutive ets-2 activity may contribute to the pathology of me-v mice by increasing expression of genes like the Bcl-x gene that promote macrophage survival.
Original languageEnglish
Pages (from-to)8026-34
Number of pages9
JournalMolecular and Cellular Biology
Volume20
Issue number21
Publication statusPublished - Nov 2000

Keywords

  • Animals
  • Apoptosis
  • Blotting, Northern
  • Blotting, Western
  • Cell Line
  • Cell Survival
  • Chromones
  • DNA-Binding Proteins
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors
  • Flow Cytometry
  • Immunohistochemistry
  • JNK Mitogen-Activated Protein Kinases
  • Macrophage Colony-Stimulating Factor
  • Macrophages
  • Membrane Proteins
  • Mice
  • Mice, Mutant Strains
  • Mitogen-Activated Protein Kinase 10
  • Mitogen-Activated Protein Kinases
  • Morpholines
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Protein Isoforms
  • Protein-Serine-Threonine Kinases
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Immunologic
  • Receptors, Lipoprotein
  • Receptors, Scavenger
  • Repressor Proteins
  • Scavenger Receptors, Class B
  • Signal Transduction
  • Threonine
  • Time Factors
  • Trans-Activators
  • Transcription Factors
  • Transfection
  • Urokinase-Type Plasminogen Activator
  • bcl-X Protein

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