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Oncogenic pathway driven by p85β: upstream signals to activate p110

Ling Rao1, Lydia W T Cheung1

  • 1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.

Molecular & Cellular Oncology
|September 18, 2020
PubMed

Insights

Phosphatidylinositol 3-kinase (PI3K) and receptor tyrosine kinase (RTK) signaling pathways show bidirectional regulation. Specifically, p85β enhances AXL receptor levels, activating PI3K signaling.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Cancer research

Background:

  • Phosphatidylinositol 3-kinase (PI3K) is a key signaling enzyme downstream of receptor tyrosine kinases (RTKs).
  • PI3K consists of regulatory (p85) and catalytic (p110) subunits, crucial for cell growth and survival.
  • RTKs, like AXL, play vital roles in cellular communication and are often implicated in cancer.

Purpose of the Study:

  • To investigate the regulatory relationship between PI3K and RTKs.
  • To elucidate the specific role of the p85β regulatory subunit of PI3K in RTK signaling.
  • To determine if PI3K and RTK pathways exhibit bidirectional cross-talk.

Main Methods:

  • Western blotting to assess protein levels of AXL and PI3K subunits.
  • Co-immunoprecipitation assays to study protein-protein interactions.
  • Cell-based assays to evaluate PI3K activation.

Main Results:

  • The p85β subunit of PI3K was found to increase the protein stability and expression of AXL, a receptor tyrosine kinase.
  • Increased AXL levels led to enhanced activation of the p110 catalytic subunit of PI3K.
  • These findings suggest a novel mechanism of positive feedback from PI3K to RTK.

Conclusions:

  • The PI3K and RTK signaling pathways are bidirectionally regulated.
  • p85β plays a critical role in stabilizing AXL, thereby promoting PI3K pathway activation.
  • This cross-talk may represent a significant mechanism in cellular processes and disease states.
Keywords:
AXLPI3Kautophagyp85protein degradation

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