Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2 Journal Article
| Authors: | 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. |
| Article Title: | Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2 |
| 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. |
| Keywords: | signal transduction; controlled study; unclassified drug; dna-binding proteins; nonhuman; animal cell; animals; cell line; sonic hedgehog protein; protein; transcription factor; rna interference; phosphorylation; animalia; transcription factors; gene expression regulation, developmental; amino acid sequence; molecular sequence data; recombinant fusion proteins; sequence alignment; protein-serine-threonine kinases; membrane protein; cytoplasm; genes, reporter; drosophila melanogaster; embryonic structures; repressor proteins; erinaceidae; drosophila proteins; receptors, g-protein-coupled; kinesin; macromolecular substances; hedgehog; cytoplasm protein; protein smoothened; humans; article; costal 2 protein; fu protein; su protein; transcription factor cubitus interruptus |
| Journal Title: | Molecular Cell |
| Volume: | 12 |
| Issue: | 5 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2003-11-01 |
| Start Page: | 1261 |
| End Page: | 1274 |
| Language: | English |
| DOI: | 10.1016/s1097-2765(03)00426-x |
| PUBMED: | 14636583 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
