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

Overview

MeSH Major

  • Biomarkers, Tumor
  • Carcinoma, Small Cell
  • DNA Helicases
  • Hypercalcemia
  • Nuclear Proteins
  • Ovarian Neoplasms
  • Transcription Factors

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

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1016/S1097-2765(03)00426-X

Additional Document Info

start page

  • 1261

end page

  • 74

volume

  • 12

number

  • 5