The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Hedgehog signal transduction by Smoothened: Pharmacologic evidence for a 2-step activation process
Open accessAbstract
The Hedgehog (Hh) signaling pathway controls growth, cell fate decisions, and morphogenesis during development. Damage to Hh transduction machinery can lead to birth defects and cancer. The transmembrane protein Smoothened (Smo) relays the Hh signal and is an important drug target in cancer. Smo enrichment in primary cilia is thought to drive activation of target genes. Using small-molecule agonists and antagonists to dissect Smo function, we find that Smo enrichment in cilia is not sufficient for signaling and a distinct second step is required for full activation. This 2-step mechanism—localization followed by activation—has direct implications for the design and use of anticancer therapeutics targeted against Smo.
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Cites
De Lean, A., Stadel, J. M., & Lefkowitz, R. J. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)79672-9 · Cited by 1,612
Vertebrate Smoothened functions at the primary cilium
Corbit, K. C., Aanstad, P., Singla, V., Norman, A. R., Stainier, D. Y. R., & Reiter, J. F. (2005) · Nature · doi:10.1038/nature04117 · Cited by 1,481
Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened
Chen, J. K., Taipale, J., Cooper, M. K., & Beachy, P. A. (2002) · Genes & Development · doi:10.1101/gad.1025302 · Cited by 1,465
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
Self-citationHedgehog signalling in the mouse requires intraflagellar transport proteins
Huangfu, D., Liu, A., Rakeman, A. S., Murcia, N. S., Niswander, L., & Anderson, K. V. (2003) · Nature · doi:10.1038/nature02061 · Cited by 1,425
Activating Smoothened mutations in sporadic basal-cell carcinoma
Xie, J., Murone, M., Luoh, S.-M., Ryan, A., Gu, Q., Zhang, C., Bonifas, J. M., Lam, C.-W., Hynes, M., Goddard, A., et al. (1998) · Nature · doi:10.1038/34201 · Cited by 1,334
Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine
Taipale, J., Chen, J. K., Cooper, M. K., Wang, B., Mann, R. K., Milenkovic, L., Scott, M. P., & Beachy, P. A. (2000) · Nature · doi:10.1038/35023008 · Cited by 1,311
Self-citationSmall molecule modulation of Smoothened activity
Chen, J. K., Taipale, J., Young, K. E., Maiti, T., & Beachy, P. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182542899 · Cited by 992
Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3
Sergina, N. V., Rausch, M., Wang, D., Blair, J., Hann, B., Shokat, K. M., & Moasser, M. M. (2007) · Nature · doi:10.1038/nature05474 · Cited by 991
Targeting the Hedgehog pathway in cancer
Rubin, L. L., & de Sauvage, F. J. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2086 · Cited by 949
Cited by
The mechanisms of Hedgehog signalling and its roles in development and disease
Briscoe, J., & Thérond, P. P. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3598 · Cited by 1,751
Wnt/β-catenin signaling in cancers and targeted therapies
Yu, F., Yu, C., Li, F., Zuo, Y., Wang, Y., Yao, L., Wu, C., Wang, C., & Ye, L. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00701-5 · Cited by 734
Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth
Kim, J., Tang, J. Y., Gong, R., Kim, J., Lee, J. J., Clemons, K. V., Chong, C. R., Chang, K. S., Fereshteh, M., Gardner, D., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.02.027 · Cited by 527
Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade
Hyman, J. M., Firestone, A. J., Heine, V. M., Zhao, Y., Ocasio, C. A., Han, K., Sun, M., Rack, P. G., Sinha, S., Wu, J. J., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907134106 · Cited by 305
Oxysterols are allosteric activators of the oncoprotein Smoothened
Nachtergaele, S., Mydock, L. K., Krishnan, K., Rammohan, J., Schlesinger, P. H., Covey, D. F., & Rohatgi, R. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.765 · Cited by 284
Self-citation
Metadata
- Authors
- Rohatgi, R., Milenkovic, L., Corcoran, R. B., & Scott, M. P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-03-03
- Volume
- 106
- Issue
- 9
- Pages
- 3196-3201
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2040182956
- Cited by
- 280
- References
- 23
- FWCI
- 10.56
- Type
- journal article
- Language
- en
- Open access
- green
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