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Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins

K Shuai1, A Ziemiecki, A F Wilks

  • 1Laboratory of Molecular Cell Biology, Rockefeller University, New York 10021-6399.

Nature
|December 9, 1993
PubMed

Insights

Interferons (IFNs) trigger signal transducer and activator of transcription (Stat) protein activation via tyrosine phosphorylation. This study suggests Janus kinase 1 (Jak1) may be the key enzyme phosphorylating Stat91 in response to IFNs and EGF.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Immunology

Background:

  • Interferons (IFNs) bind cell surface receptors, initiating signal transduction.
  • Tyrosine phosphorylation of signal transducers and activators of transcription (Stat) proteins is a key early event.
  • Specific tyrosine kinases, Tyrosine kinase-2 (Tyk2) and Janus kinase 2 (Jak2), are implicated in IFN-alpha and IFN-gamma signaling, respectively.

Purpose of the Study:

  • To investigate tyrosine phosphorylation events on Stat and Jak proteins.
  • To determine the role of specific kinases in interferon and epidermal growth factor (EGF) signaling pathways.

Main Methods:

  • Cell treatment with IFN-alpha, IFN-gamma, and EGF.
  • Analysis of tyrosine phosphorylation in Stat and Jak proteins.
  • Comparison of kinase activation by different ligands.

Main Results:

  • Stat91 is phosphorylated on Tyr701 by IFN-alpha, IFN-gamma, and EGF.
  • Janus kinase 1 (Jak1) is tyrosine phosphorylated by all three ligands.
  • Each ligand activates at least one distinct kinase.

Conclusions:

  • Jak1 is a potential candidate enzyme for phosphorylating Tyr701 in Stat91.
  • Jak1 plays a role in signaling pathways activated by IFNs and EGF.
  • Interferon and growth factor signaling pathways share common components and mechanisms.

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