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

Lawrence Lum, Chi Zhang, Sekyung Oh, Randall K. Mann, Doris P. Von Kessler, Jussi Taipale, Frances Weis-Garcia, Ruoyu Gong, Baolin Wang, Philip A. Beachy

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184 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1261-1274
Number of pages14
JournalMolecular cell
Volume12
Issue number5
DOIs
StatePublished - Nov 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Lum, L., Zhang, C., Oh, S., Mann, R. K., Von Kessler, D. P., Taipale, J., Weis-Garcia, F., Gong, R., Wang, B., & Beachy, P. A. (2003). Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2. Molecular cell, 12(5), 1261-1274. https://doi.org/10.1016/S1097-2765(03)00426-X