c-Fes tyrosine kinase binds to and activates STAT3 after granulocyte-macrophage colony-stimulating factor stimulation

Woong Yang Park, Jung Hyuck Ahn, Ricardo A. Feldman, Jeong Sun Seo

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25 Scopus citations


Granulocyte-macrophage colony stimulating factor (GM-CSF) induces proliferation and maturation of myeloid progenitor cells and also activates neutrophils. In order to investigate the pleiotropic effects of GM-CSF stimulation, we examined the signaling pathways of protein tyrosine kinases (PTKs) and signal transducers and activators of transcription (STATs) in GMCSF-dependent proliferation of leukemia cells. Using TF-1, a GM-CSF-dependent human erythroleukemia cell line, we found that GM-CSF enhanced DNA-binding and tyrosine phosphorylation of STAT3. GM-CSF receptor (GM-CSFR) and c-Fes tyrosine kinase were also activated upon GM-CSF stimulation. Furthermore, c-Fes formed a complex with STAT3. Experiments using a c-Fes mutant that lacked tyrosine kinase activity revealed that the activation of STAT3 is kinase-dependent, but that the c-Fes-STAT3 interaction is not affected by c-Fes tyrosine kinase activity. The results suggest that STAT3 is activated by c-Fes tyrosine kinase through direct interaction during hematopoietic cell proliferation induced by GM-CSF.

Original languageEnglish
Pages (from-to)29-37
Number of pages9
JournalCancer Letters
Issue number1
StatePublished - 3 Jul 1998

Bibliographical note

Funding Information:
We would like to thank D.-Y. Jung for her technical assistance and G. Hoschek for carefully reading this manuscript. This study was supported in part by a grant to J.-S.S. from the Ministry of Education (No. 95-095, 1995) and by the Korean Science and Engineering Foundation (KOSEF) through the Cancer Research Center at Seoul National University (CRC95K2-0401-06-00-3, 1995) and from the Han Project of the Ministry of Science and Technology, Korea (No. 08-01-06, 1996). This study was also supported by a grant to R.A.F. from the National Cancer Institute, National Institute of Health, USA (CA 55293).


  • GM-CSF
  • Interaction
  • STAT
  • Tyrosine phosphorylation
  • c-Fes


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