Regulation of Drosophila tracheal system development by protein kinase B

J Jin1, N Anthopoulos, B Wetsch

  • 1Division of Cellular and Molecular Biology, Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, Toronto, Ontario, M5G 2M9, Canada.

Developmental Cell
|December 13, 2001
PubMed

Insights

Protein kinase B (PKB) directly phosphorylates the trachealess (Trh) transcription factor, enabling its nuclear entry. This PKB-mediated Trh activation is crucial for tracheal branching morphogenesis in Drosophila.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Cell Signaling

Background:

  • Protein kinase B (PKB/Akt) is a key regulator of cell survival and is implicated in human cancers.
  • PKB/Akt is dependent on phosphatidylinositol 3'-kinase (PI3'K) signaling pathways.
  • Understanding PKB/Akt targets is crucial for elucidating its role in tumorigenesis.

Purpose of the Study:

  • To identify novel targets of Protein kinase B (PKB/Akt) using a genetic screen in Drosophila.
  • To investigate the functional relationship between PKB/Akt and the trachealess (Trh) gene.
  • To elucidate the molecular mechanism by which PKB/Akt regulates branching morphogenesis.

Main Methods:

  • Genetic screening in Drosophila to identify PKB/Akt interacting genes.
  • Biochemical assays to confirm direct interactions and phosphorylation events.
  • Transgenic approaches to study gene function and localization in vivo.

Main Results:

  • A genetic screen identified trachealess (trh) as a gene interacting with PKB/Akt.
  • Trachealess (Trh) encodes a bHLH-PAS transcription factor essential for tracheal development.
  • PKB/Akt directly phosphorylates Trh at serine 665, which is required for its nuclear localization and activation.
  • This phosphorylation event is critical for regulating tracheal branching morphogenesis.

Conclusions:

  • Direct phosphorylation of Trh by PKB/Akt is a key regulatory mechanism controlling tracheal development.
  • This finding reveals a novel link between PI3'K/PKB signaling and developmental processes regulated by Trh.
  • The identified PKB/Akt-Trh pathway represents a potential target for therapeutic intervention in related human diseases.

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