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In vitro activation of Stat3 by epidermal growth factor receptor kinase

O K Park1, T S Schaefer, D Nathans

  • 1Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 26, 1996
PubMed

Insights

Signal transducer and activator of transcription (Stat) proteins are activated by growth factors. Epidermal growth factor receptor kinase directly phosphorylates and activates Stat3 proteins in vitro.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Transcription Factors

Background:

  • Signal transducer and activator of transcription (Stat) proteins are key transcription factors activated by cytokines and growth factors.
  • Activation pathways differ: JAK kinases mediate cytokine receptor signaling, while growth factor receptor tyrosine kinases may activate Stats directly or indirectly.

Purpose of the Study:

  • To investigate the direct activation of Stat proteins by the epidermal growth factor receptor (EGFR) kinase.
  • To determine if EGFR kinase can directly phosphorylate and activate Stat proteins in vitro.

Main Methods:

  • Purified Stat3 alpha and Stat3 beta proteins were used.
  • Recombinant epidermal growth factor receptor kinase was produced in Sf9 insect cells.
  • In vitro kinase assays were performed to assess Stat protein phosphorylation and DNA binding activity.

Main Results:

  • Stat3 proteins formed a stable complex with the EGFR kinase.
  • EGFR kinase directly phosphorylated Stat3 proteins on tyrosine residues, leading to activation for DNA binding.
  • Phosphorylated Stat3 beta exhibited significantly higher DNA binding activity compared to phosphorylated Stat3 alpha.

Conclusions:

  • Stat3 isoforms can be directly phosphorylated and activated by the epidermal growth factor receptor kinase in vitro.
  • This finding supports a direct role for EGFR in Stat protein activation, independent of JAK kinases.

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