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Activation of STAT3 by the c-Fes protein-tyrosine kinase

K L Nelson1, J A Rogers, T L Bowman

  • 1Eppley Institute for Research in Cancer and Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.

The Journal of Biological Chemistry
|April 18, 1998
PubMed

Insights

The c-Fes tyrosine kinase potently activates STAT3, a key transcription factor. This finding suggests c-Fes and STAT3 may cooperate in myeloid differentiation signaling pathways.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Oncology

Background:

  • Signal transducers and activators of transcription (STATs) are crucial transcription factors activated by tyrosine phosphorylation, often via cytokine signaling.
  • Oncogenic tyrosine kinases like v-Src, v-Abl, and v-Fps can activate STATs, implying roles for their cellular counterparts in normal STAT activation.

Purpose of the Study:

  • To investigate the role of c-Fes, the human homolog of v-Fps, in activating STAT transcription factors.
  • To determine if c-Fes specifically activates STAT3 and/or STAT5 and to explore the mechanism of activation.

Main Methods:

  • Transient transfection of human 293T cells and Sf-9 insect cells with STAT3, STAT5, and c-Fes constructs.
  • Assessing STAT DNA binding activity using gel-shift assays.
  • Analyzing tyrosine phosphorylation of STAT proteins.
  • Utilizing Bcr-Abl tyrosine kinase as a positive control in Sf-9 cells.

Main Results:

  • c-Fes strongly activated STAT3 DNA binding activity in both human and insect cell systems.
  • A modest activation of STAT5 by c-Fes was observed in human cells, with no activation in insect cells, suggesting STAT3 selectivity.
  • c-Fes induced significant tyrosine phosphorylation of STAT3, correlating with enhanced DNA binding.
  • Bcr-Abl tyrosine kinase activated both STAT3 and STAT5 in Sf-9 cells.

Conclusions:

  • The non-receptor tyrosine kinase c-Fes is a potent activator of STAT3.
  • c-Fes-mediated STAT3 activation occurs independently of endogenous mammalian kinases.
  • These findings suggest a cooperative role for c-Fes and STAT3 in promoting myeloid differentiation signaling, particularly in response to hematopoietic cytokines.

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