Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2
- PMID: 14636583
- DOI: 10.1016/s1097-2765(03)00426-x
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.
Similar articles
-
Phosphorylation of the atypical kinesin Costal2 by the kinase Fused induces the partial disassembly of the Smoothened-Fused-Costal2-Cubitus interruptus complex in Hedgehog signalling.Development. 2007 Oct;134(20):3677-89. doi: 10.1242/dev.011577. Epub 2007 Sep 19. Development. 2007. PMID: 17881487
-
Stability and association of Smoothened, Costal2 and Fused with Cubitus interruptus are regulated by Hedgehog.Nat Cell Biol. 2003 Oct;5(10):907-13. doi: 10.1038/ncb1052. Epub 2003 Oct 1. Nat Cell Biol. 2003. PMID: 14523402
-
Fused-Costal2 protein complex regulates Hedgehog-induced Smo phosphorylation and cell-surface accumulation.Genes Dev. 2007 Aug 1;21(15):1949-63. doi: 10.1101/gad.1557407. Genes Dev. 2007. PMID: 17671093 Free PMC article.
-
Regulation of Hedgehog signaling: a complex story.Biochem Pharmacol. 2004 Mar 1;67(5):805-14. doi: 10.1016/j.bcp.2004.01.002. Biochem Pharmacol. 2004. PMID: 15104233 Free PMC article. Review.
-
Hedgehog signaling: Costal-2 bridges the transduction gap.Curr Biol. 2004 Jan 20;14(2):R67-9. doi: 10.1016/j.cub.2003.12.047. Curr Biol. 2004. PMID: 14738752 Review.
Cited by
-
Broad-minded links cell cycle-related kinase to cilia assembly and hedgehog signal transduction.Dev Cell. 2010 Feb 16;18(2):237-47. doi: 10.1016/j.devcel.2009.12.014. Dev Cell. 2010. PMID: 20159594 Free PMC article.
-
Hedgehog activates fused through phosphorylation to elicit a full spectrum of pathway responses.Dev Cell. 2011 Jun 14;20(6):802-14. doi: 10.1016/j.devcel.2011.04.020. Dev Cell. 2011. PMID: 21664578 Free PMC article.
-
Canonical and non-canonical Hedgehog signalling and the control of metabolism.Semin Cell Dev Biol. 2014 Sep;33:81-92. doi: 10.1016/j.semcdb.2014.05.007. Epub 2014 May 23. Semin Cell Dev Biol. 2014. PMID: 24862854 Free PMC article. Review.
-
Hedgehog on the Move: Glypican-Regulated Transport and Gradient Formation in Drosophila.Cells. 2024 Feb 27;13(5):418. doi: 10.3390/cells13050418. Cells. 2024. PMID: 38474382 Free PMC article. Review.
-
Regulation of Ci-SCFSlimb binding, Ci proteolysis, and hedgehog pathway activity by Ci phosphorylation.Dev Cell. 2007 Oct;13(4):481-95. doi: 10.1016/j.devcel.2007.09.006. Dev Cell. 2007. PMID: 17925225 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous
