Granulocyte-macrophage colony-stimulating factor stimulation results in phosphorylation of cAMP response element-binding protein through activation of pp90RSK

Blood. 2000 Apr 15;95(8):2552-8.

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) activates several kinases and transcription factors through interaction with a heterodimeric receptor complex. We previously demonstrated that phosphorylation of the cyclic adenosine monophosphate (cAMP) response element-binding protein, CREB, occurs through a protein kinase A-independent pathway and is required for GM-CSF-induced transcriptional activation of the immediate early gene, early growth response-1 (egr-1). Recent reports indicate that receptor tyrosine kinases can induce CREB phosphorylation through activation of pp90RSK. We performed immune complex kinase assays in the human myeloid leukemic cell line, TF-1, which revealed that GM-CSF induced pp90RSK activation and phosphorylation of CREB within 5 minutes of stimulation. Transfection with the kinase-defective pp90RSK expression plasmid demonstrated a statistically significant decrease in transcriptional activation of a -116 CAT/egr-1 promoter construct in response to GM-CSF. Furthermore, activation of pp90RSK, CREB and egr-1 in GM-CSF-treated cells was inhibited by the presence of the inhibitor, PD98059. In this study, we report that GM-CSF induces CREB phosphorylation and egr-1 transcription by activating pp90RSK through an MEK-dependent signaling pathway. (Blood. 2000;95:2552-2558)

Publication types

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

MeSH terms

  • Cyclic AMP Response Element-Binding Protein / physiology*
  • Enzyme Activation
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology
  • Humans
  • Phosphorylation
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
  • Ribosomal Protein S6 Kinases / physiology*
  • Signal Transduction / drug effects*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Ribosomal Protein S6 Kinases