Genetic dissection of the Drosophila Cubitus interruptus signaling complex

Mark A. Lefers, Q. Tian Wang, Robert A. Holmgren

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Much of our understanding of the Hedgehog (Hh) signaling pathway comes from Drosophila, where a gradient of Hh signaling regulates the function of the transcription factor Cubitus interruptus (Ci) at three levels: protein stabilization, nuclear import, and activation. Regulation of Ci occurs in a cytoplasmic complex containing Ci, the kinesin-like protein Costal-2 (Cos2), the serine-threonine kinase Fused (Fu), and the Suppressor of Fused [Su(fu)] protein. The mechanisms by which this complex responds to different levels of Hh signaling and establishes distinct domains of gene expression are not fully understood. By sequentially mutating components from the Ci signaling complex, their roles in each aspect of Ci regulation can be analyzed. The Cos2-Ci core complex is able to mediate Hh-regulated activation of Ci but is insufficient to regulate nuclear import and cleavage. Addition of Su(fu) to the core complex blocks nuclear import while the addition of Fu restores Hh regulation of Ci nuclear import and proteolytic cleavage. Fu participates in two partially redundant pathways to regulate Ci nuclear import; the kinase function plays a positive role by inhibiting Su(fu), and the regulatory domain plays a negative role in conjunction with Cos2.

Original languageEnglish (US)
Pages (from-to)411-420
Number of pages10
JournalDevelopmental Biology
Volume236
Issue number2
DOIs
StatePublished - Aug 15 2001

Keywords

  • Ci
  • Fu
  • Hedgehog
  • Nuclear import
  • Pattern formation
  • Signal transduction
  • Su(fu)

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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