Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2. Academic Article uri icon

Overview

MeSH

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cytoplasm
  • DNA-Binding Proteins
  • Drosophila melanogaster
  • Embryonic Structures
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Hedgehog Proteins
  • Humans
  • Macromolecular Substances
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • RNA Interference
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Sequence Alignment
  • Transcription Factors

MeSH Major

  • Drosophila Proteins
  • Kinesin
  • Receptors, G-Protein-Coupled
  • Signal Transduction

abstract

  • The seven-transmembrane protein Smoothened (Smo) transduces extracellular activation of the Hedgehog (Hh) pathway by an unknown mechanism to increase transcriptional activity of the latent cytoplasmic transcription factor Ci (Cubitus interruptus). Here, we present evidence that Smo associates directly with a Ci-containing complex that is scaffolded and stabilized by the atypical kinesin, Costal-2 (Cos2). This complex constitutively suppresses pathway activity, but Hh signaling reverses its regulatory effect to promote Ci-mediated transcription. In response to Hh activation of Smo, Cos2 mediates accumulation and phosphorylation of Smo at the membrane as well as phosphorylation of the cytoplasmic components Fu and Su(fu). Positive response of Cos2 to Hh stimulation requires a portion of the Smo cytoplasmic tail and the Cos2 cargo domain, which interacts directly with Smo.

publication date

  • November 2003

has subject area

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cytoplasm
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Drosophila melanogaster
  • Embryonic Structures
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Hedgehog Proteins
  • Humans
  • Kinesin
  • Macromolecular Substances
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • RNA Interference
  • Receptors, G-Protein-Coupled
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Sequence Alignment
  • Signal Transduction
  • Transcription Factors

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 14636583

Additional Document Info

start page

  • 1261

end page

  • 1274

volume

  • 12

number

  • 5