The effects of GM-CSF, steel factor and MIP-1α on the expression and activation of Cdc25A phosphatase in mo7e cells

Suzanna Reid, Hal E. Broxmeyer

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Active cyclin-dependent kinases (CDKs) are required for progression through the G1 phase of the cell cycle and entry into S phase. Activity of G1 CDKs is controlled by mechanisms including phosphorylation of Thr14 and Tyr15 residues. Removal of inhibitory phosphates on these amino acid residues is required for G1 CDK activation, and is mediated by the Cdc25A phosphatase. Regulation of active Cdc25A phosphatase levels may be important for the proliferation of hematopoietic progenitor cells, effects assessed in the human growth-factor-dependent cell line Mo7e. Constitutive Cdc25A protein levels were enhanced with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus steel factor (SF). Cdc25A is thought to exert its activity in the nucleus, and nuclear protein levels of Cdc25A were also enhanced with GM-CSF and SF. GM-CSF plus SF promote synergistic growth of Mo7e cells. Pretreatment with macrophage inflammatory protein (MIP-1α) inhibited GM-CSF- plus SF-induced growth and upregulation of Cdc25A protein levels. Stimulation with GM-CSF and SF also rapidly increased Cdc25A phosphatase activity, an effect suppressed by MIP-1α. A concomitant inhibition of increased CDK4 kinase activity correlated with increased phosphotyrosine levels on CDK4 when cells were pretreated with MIP-1α prior to GM-CSF and SF. These data suggest that Cdc25A expression and activity are regulated during proliferation of Mo7e cells.

Original languageEnglish (US)
Pages (from-to)129-138
Number of pages10
JournalCytokines, Cellular and Molecular Therapy
Volume5
Issue number3
StatePublished - Sep 1999

Keywords

  • Cell proliferation
  • GM-CSF
  • MIP-1α
  • Mo7e
  • Steel factor

ASJC Scopus subject areas

  • Pharmacology
  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'The effects of GM-CSF, steel factor and MIP-1α on the expression and activation of Cdc25A phosphatase in mo7e cells'. Together they form a unique fingerprint.

Cite this