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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Published on: July 17, 2019

RAKing in AKT: a tumor suppressor function for the intracellular tyrosine kinase FRK

Patrick M Brauer1, Angela L Tyner

  • 1Department of Biochemistry and Molecular Genetics, University of Illinois College of Medicine, Chicago, IL 60607, USA.

Cell Cycle (Georgetown, Tex.)
|August 5, 2009
PubMed

Insights

Fyn related kinase (FRK) phosphorylates the tumor suppressor PTEN, inhibiting AKT signaling and breast cancer cell growth. FRK acts as a tumor suppressor in mammary cells, contrasting with PTK6

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Fyn related kinase (FRK) is a tyrosine kinase involved in epithelial cell regulation.
  • FRK and PTK6 are related kinases with distinct gene structures from Src family kinases.
  • Both kinases are expressed in melanoma, breast cancer cells, and normal intestinal epithelium.

Purpose of the Study:

  • To investigate the role of FRK in regulating the tumor suppressor PTEN.
  • To understand FRK's impact on AKT signaling and breast cancer tumorgenicity.
  • To compare the functions of FRK and PTK6 in different cellular contexts.

Main Methods:

  • Investigated FRK's phosphorylation of PTEN (phosphatase and tensin homolog deleted from chromosome 10).
  • Assessed the effect of FRK-mediated PTEN phosphorylation on PTEN's association with NEDD4-1.
  • Utilized xenograft models to evaluate FRK's effect on breast cancer cell tumorgenicity.

Main Results:

  • FRK phosphorylates PTEN, suppressing its association with NEDD4-1 and subsequent degradation.
  • FRK acts as a positive regulator of PTEN, leading to suppressed AKT signaling.
  • FRK inhibits breast cancer cell tumorgenicity in vivo and exhibits tumor suppressor functions in mammary cells.

Conclusions:

  • FRK plays a critical role in suppressing AKT signaling by stabilizing PTEN.
  • FRK functions as a tumor suppressor in mammary gland cells, with its loss correlating with some breast tumors.
  • FRK and PTK6 exhibit context-dependent functions, differentially regulating AKT signaling in normal versus cancerous tissues.

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