A gradient of Cactus protein degradation establishes dorsoventral polarity in the Drosophila embryo

Michael Reach, Rene L. Galindo, Par Towb, Jerry L. Allen, Michael Karin, Steven A. Wasserman

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Dorsoventral polarity in the Drosophila embryo is established by a signaling pathway active on the ventral and ventrolateral surfaces of the embryo. Signal transduction via the protein kinase Pelle frees the Rel-related protein Dorsal from its cytoplasmic inhibitor Cactus, allowing Dorsal to translocate into ventral and ventrolateral nuclei and direct gene expression. Here, we show by immunochemical analyses that Pelle-mediated signaling induces the spatially graded degradation of Cactus. Using a tissue culture system which reconstitutes Pelle-dependent Cactus degradation, we show that a motif in Cactus resembling the sites of signal-dependent phosphorylation in the vertebrate homologs IκB-α and IκB-β is essential for Pelle-induced Cactus degradation. Substitution of four serines within this motif with nonphosphorylatable alanine residues generated a mutant Cactus that still functions as a Dorsal inhibitor but is resistant to induced degradation. Injection of RNA encoding this altered form of Cactus has a dominant negative effect on establishment of dorsoventral polarity in the embryo. We conclude that dorsoventral signaling results in a Cactus concentration gradient and propose that signal-dependent phosphorylation directs the spatially regulated proteolysis of Cactus protein.

Original languageEnglish (US)
Pages (from-to)353-364
Number of pages12
JournalDevelopmental Biology
Volume180
Issue number1
DOIs
StatePublished - Nov 25 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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