The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Hedgehog Pathway Modulation by Multiple Lipid Binding Sites on the Smoothened Effector of Signal Response
Open accessAbstract
Summary Hedgehog (Hh) signaling during development and in postembryonic tissues requires activation of the 7TM oncoprotein Smoothened (Smo), by mechanisms that may involve endogenous lipidic modulators. Exogenous Smo ligands previously identified include the plant sterol cyclopamine (and its therapeutically useful synthetic mimics) and hydroxylated cholesterol derivatives (oxysterols); Smo is also highly sensitive to cellular sterol levels. The relationships between these effects are unclear because the relevant Smo structural determinants are unknown. We identify the conserved extracellular cysteine rich domain (CRD) as the site of action for oxysterols on Smo, involving residues structurally analogous to those contacting the Wnt lipid adduct in the homologous Frizzled CRD; this modulatory effect is distinct from that of cyclopamine mimics, from Hh-mediated regulation, and from the permissive action of cellular sterol pools. These results imply that Hh pathway activity is sensitive to lipid binding at several Smo sites, suggesting mechanisms for tuning by multiple physiological inputs.
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Citations
Cites
Wnt/β-catenin signaling and disease
Clevers, H., & Nusse, R. (2012) · Cell · doi:10.1016/j.cell.2012.05.012 · Cited by 5,554
Patched1 Regulates Hedgehog Signaling at the Primary Cilium
Rohatgi, R., Milenkovic, L., & Scott, M. P. (2007) · Science · doi:10.1126/science.1139740 · Cited by 1,426
Patched acts catalytically to suppress the activity of Smoothened
Taipale, J., Cooper, M. K., Maiti, T., & Beachy, P. A. (2002) · Nature · doi:10.1038/nature00989 · Cited by 794 · cited 5×
“…Smo constitutive activity is strongly suppressed by substoichiometric amounts of Ptch1, and Smo activity is restored by treatment with Hh protein (Taipale et al., 2002), illustrating that the underlying inhibitory effects are dependent on Ptch1 activity rather than nonspecific consequences of…”
BackgroundInfluentialSelf-citationA Smoothened-Evc2 Complex Transduces the Hedgehog Signal at Primary Cilia
Dorn, K. V., Hughes, C. E., & Rohatgi, R. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.07.004 · Cited by 174
Cited by
Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling
Huang, P., Nedelcu, D., Watanabe, M., Jao, C., Kim, Y., Liu, J., & Salic, A. (2016) · Cell · doi:10.1016/j.cell.2016.08.003 · Cited by 377
Identification of recurrent SMO and BRAF mutations in ameloblastomas
Sweeney, R. T., McClary, A. C., Myers, B. R., Biscocho, J., Neahring, L., Kwei, K. A., Qu, K., Gong, X., Ng, T., Jones, C. D., et al. (2014) · Nature Genetics · doi:10.1038/ng.2986 · Cited by 366
Self-citationOpen Sesame: How Transition Fibers and the Transition Zone Control Ciliary Composition
Garcia-Gonzalo, F. R., & Reiter, J. F. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028134 · Cited by 290
Structural Basis for Cholesterol Transport-like Activity of the Hedgehog Receptor Patched
Zhang, Y., Bulkley, D. P., Xin, Y., Roberts, K. J., Asarnow, D. E., Sharma, A., Myers, B. R., Cho, W., Cheng, Y., & Beachy, P. A. (2018) · Cell · doi:10.1016/j.cell.2018.10.026 · Cited by 239
Self-citationStructural Basis of Smoothened Activation in Hedgehog Signaling
Huang, P., Zheng, S., Wierbowski, B. M., Kim, Y., Nedelcu, D., Aravena, L., Liu, J., Kruse, A. C., & Salic, A. (2018) · Cell · doi:10.1016/j.cell.2018.04.029 · Cited by 176
Metadata
- Authors
- Myers, B. R., Sever, N., Chong, Y. C., Kim, J., Belani, J. D., Rychnovsky, S., Bazan, J. F., & Beachy, P. A.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 26
- Issue
- 4
- Pages
- 346-357
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W1966998932
- Cited by
- 200
- References
- 4
- FWCI
- 8.20
- Type
- journal article
- Language
- en
- Open access
- bronze
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