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Abelson family kinases regulate Frizzled planar cell polarity signaling via Dsh phosphorylation

Jaskirat Singh1, Wang A Yanfeng, Luca Grumolato

  • 1Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.

Genes & Development
|September 15, 2010
PubMed

Insights

Abelson (Abl) kinases regulate planar cell polarity (PCP) signaling by phosphorylating Dishevelled (Dsh). This phosphorylation is crucial for Dsh function in PCP pathways, conserved across species.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Signal Transduction

Background:

  • Abelson (Abl) tyrosine kinases are involved in cell functions like morphogenesis and oncogenesis.
  • Planar cell polarity (PCP) signaling pathways regulate cell organization and tissue polarity.

Purpose of the Study:

  • To investigate the role of Drosophila Abl (dAbl) in Frizzled/PCP signaling.
  • To elucidate the molecular mechanism by which Abl kinases regulate PCP.
  • To determine if this role is conserved in mammals.

Main Methods:

  • Candidate gene approach to identify modulators of Frizzled/PCP signaling in Drosophila.
  • Genetic dissection of Abl's function in photoreceptor R3 specification.
  • Molecular analysis of Abl-Dishevelled interaction and phosphorylation.
  • Study of Abl-deficient mouse embryonic fibroblasts (MEFs).

Main Results:

  • Drosophila Abl (dAbl) positively regulates Frizzled/Dishevelled (Dsh) PCP pathway.
  • dAbl phosphorylates Dsh on Tyr473, which is critical for PCP signaling and membrane association.
  • Abl-deficient MEFs show reduced Dvl2 phosphorylation and altered Dvl2 localization, impacting PCP.
  • Neither Drosophila nor mouse Abl affects canonical Wnt signaling.

Conclusions:

  • Abl family kinases are conserved positive regulators of Frizzled-Dishevelled/PCP signaling.
  • Abl-mediated phosphorylation of Dishevelled is a key mechanism for its PCP function.
  • Abl kinases specifically modulate PCP signaling, distinct from canonical Wnt signaling.

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