Granulocyte-macrophage colony-stimulating factor induces the transcriptional activation of egr-1 through a protein kinase A-independent signaling pathway

J Biol Chem. 1995 Dec 22;270(51):30271-3. doi: 10.1074/jbc.270.51.30271.


Granulocyte-macrophage colony-stimulating factor (GM-CSF) rapidly and transiently induces the transcriptional activation of the early growth response gene-1 (egr-1) in the human factor-dependent myeloid leukemic cell line, TF-1. We previously demonstrated that the cAMP response element (CRE) is required for GM-CSF-induced egr-1 expression and that phosphorylation of CREB on serine 133 plays a critical role during GM-CSF signal transduction. To determine whether GM-CSF activates signaling pathways through a protein kinase A-dependent or -independent pathway, we measured cAMP levels following GM-CSF or forskolin treatment of TF-1 cells. Forskolin but not GM-CSF stimulation resulted in an increase in cAMP levels. Transient transfection assays with TF-1 cells were also performed with a -116-nucleotide egr-1 promoter construct and the protein kinase inhibitor, PKI. Although PKI inhibited forskolin induction of the -116-nucleotide construct, it did not affect GM-CSF stimulation of this construct. In the present study, we demonstrated that GM-CSF induces egr-1 expression through a protein kinase A-independent pathway.

Publication types

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

MeSH terms

  • Cell Line
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • DNA-Binding Proteins / biosynthesis*
  • Early Growth Response Protein 1
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Immediate-Early Proteins*
  • Kinetics
  • Leukemia, Myeloid
  • Promoter Regions, Genetic
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / pharmacology
  • Signal Transduction*
  • Transcription Factors / biosynthesis*
  • Transcriptional Activation / drug effects*
  • Transfection
  • Tumor Cells, Cultured
  • Zinc Fingers
  • beta-Galactosidase / biosynthesis


  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Enzyme Inhibitors
  • Immediate-Early Proteins
  • Recombinant Proteins
  • Transcription Factors
  • Colforsin
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • beta-Galactosidase