Granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced STAT5 activation and target-gene expression during human monocyte/macrophage differentiation

J Leukoc Biol. 2002 Mar;71(3):511-9.

Abstract

GM-CSF signals through JAK2 and STAT5 and stimulates the expression of STAT5 target genes, such as pim-1 and CIS. Analyzed by EMSA, GM-CSF stimulation led to much stronger STAT5 DNA-binding to pim-1 or CIS GAS elements in primary human monocytes compared with mature macrophages. Similarly, GM-CSF-induced expression of pim-1 and CIS mRNAs was much stronger in monocytes. These differencies were not a result of downregulation of the GM-CSF receptor system or STAT5 expression, because monocytes and macrophages readily expressed GM-CSF receptor, JAK2, STAT5A, and STAT5B mRNAs and proteins. Monocytes expressed significant amounts of truncated STAT5 forms that took part in STAT5-DNA complex formation in GM-CSF-stimulated monocytes. This resulted in faster moving STAT5 complexes compared with macrophages in EMSA. Our results demonstrate that STAT5 isoform expression, GM-CSF-induced STAT5 activation, and STAT5 target-gene expression are altered significantly during monocyte/macrophage differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Immediate-Early Proteins / genetics
  • Macrophages / cytology
  • Macrophages / physiology*
  • Milk Proteins*
  • Monocytes / cytology
  • Monocytes / physiology*
  • Protein-Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-pim-1
  • STAT5 Transcription Factor
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators / physiology*
  • Tumor Suppressor Proteins

Substances

  • DNA-Binding Proteins
  • Immediate-Early Proteins
  • Milk Proteins
  • Proto-Oncogene Proteins
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • STAT5B protein, human
  • Suppressor of Cytokine Signaling Proteins
  • Trans-Activators
  • Tumor Suppressor Proteins
  • cytokine inducible SH2-containing protein
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • PIM1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-pim-1