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

91 Citations (Scopus)

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

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Cactaceae
Proteolysis
Drosophila
Embryonic Structures
Transcription Factor RelB
Phosphorylation
Alanine
Protein Kinases
Serine
Vertebrates
Signal Transduction
RNA
Gene Expression

ASJC Scopus subject areas

  • Developmental Biology

Cite this

A gradient of Cactus protein degradation establishes dorsoventral polarity in the Drosophila embryo. / Reach, Michael; Galindo, Rene L.; Towb, Par; Allen, Jerry L.; Karin, Michael; Wasserman, Steven A.

In: Developmental Biology, Vol. 180, No. 1, 25.11.1996, p. 353-364.

Research output: Contribution to journalArticle

Reach, Michael ; Galindo, Rene L. ; Towb, Par ; Allen, Jerry L. ; Karin, Michael ; Wasserman, Steven A. / A gradient of Cactus protein degradation establishes dorsoventral polarity in the Drosophila embryo. In: Developmental Biology. 1996 ; Vol. 180, No. 1. pp. 353-364.
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