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Complexes of p21RAS with JUN N-terminal kinase and JUN proteins

V Adler1, M R Pincus, P W Brandt-Rauf

  • 1Molecular Carcinogenesis Program, American Health Foundation, Valhalla, NY 10595, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 7, 1995
PubMed

Insights

RAS p21 protein enhances JUN phosphorylation by JUN N-terminal kinase (JNK). Both wild-type and oncogenic p21 proteins bind to JNK and JUN, suggesting specific interactions crucial for cell signaling pathways.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Oncogenesis

Background:

  • RAS gene-encoded p21 protein plays a role in cellular signaling.
  • JUN N-terminal kinase (JNK) is a key kinase in stress-activated pathways.
  • Phosphorylation of JUN by JNK is a critical regulatory event.

Purpose of the Study:

  • To investigate the interaction between RAS p21 protein and the JNK/JUN pathway.
  • To determine if RAS p21 protein modulates JNK activity and JUN phosphorylation.
  • To elucidate the binding specificities between p21, JNK, and JUN.

Main Methods:

  • In vitro kinase assays to measure JUN phosphorylation.
  • Co-immunoprecipitation to assess protein-protein interactions.
  • Binding studies using purified proteins and cell extracts.

Main Results:

  • RAS p21 protein (both wild-type and oncogenic Val-12) increases JUN phosphorylation by JNK in a dose-dependent manner.
  • Oncogenic p21 protein demonstrates higher potency in this effect.
  • Both normal and oncogenic p21 proteins bind directly to JNK and JUN, with binding influenced by GTP and specific JUN domains.
  • Specific p21 peptides inhibit p21 binding to JNK and JUN, indicating distinct interaction sites.

Conclusions:

  • RAS p21 protein specifically interacts with both JNK and JUN.
  • These interactions likely mediate the observed increase in JUN phosphorylation.
  • The findings suggest a novel regulatory mechanism involving RAS p21 in the JNK/JUN signaling pathway, with implications for cancer biology.

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