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Science 18 June 2004: Vol. 304. no. 5678, pp. 1755 - 1759 DOI: 10.1126/science.1098020
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Review
The Hedgehog Response Network: Sensors, Switches, and Routers
Lawrence Lum and
Philip A. Beachy*
The Hedgehog (Hh) signaling pathway is intimately linked to cell growth and differentiation, with normal roles in embryonic pattern formation and adult tissue homeostasis and pathological roles in tumor initiation and growth. Recent advances in our understanding of Hh response have resulted from the identification of new pathway components and new mechanisms of action for old pathway components. The most striking new finding is that signal transmission from membrane to cytoplasm proceeds through recruitment, by the seven-transmembrane protein Smoothened, of an atypical kinesin, which routes pathway activation by interaction with other components of a complex that includes the latent zinc finger transcription factor, Ci.
Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
* To whom correspondence should be addressed. E-mail: pbeachy{at}jhmi.edu
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| Abstract »
| Full Text »
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| Abstract »
| Full Text »
| PDF »
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133, 2001-2010
| Abstract »
| Full Text »
| PDF »
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98, 1002-1013
| Abstract »
| Full Text »
| PDF »
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- Y. Li, H. Zhang, Y. Litingtung, and C. Chiang (2006)
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103, 6548-6553
| Abstract »
| Full Text »
| PDF »
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103, 3244-3249
| Abstract »
| Full Text »
| PDF »
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| Abstract »
| Full Text »
| PDF »
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- M. H. Price, D. M. Roberts, B. M. McCartney, E. Jezuit, and M. Peifer (2006)
J. Cell Sci.
119, 403-415
| Abstract »
| Full Text »
| PDF »
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- E. G. Huntzicker, I. S. Estay, H. Zhen, L. A. Lokteva, P. K. Jackson, and A. E. Oro (2006)
Genes & Dev.
20, 276-281
| Abstract »
| Full Text »
| PDF »
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- T. Sheng, S. Chi, X. Zhang, and J. Xie (2006)
J. Biol. Chem.
281, 9-12
| Abstract »
| Full Text »
| PDF »
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- M. Ohta, K. Tateishi, F. Kanai, H. Watabe, S. Kondo, B. Guleng, Y. Tanaka, Y. Asaoka, A. Jazag, J. Imamura, et al. (2005)
Cancer Res.
65, 10822-10829
| Abstract »
| Full Text »
| PDF »
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- L. Koziel, M. Wuelling, S. Schneider, and A. Vortkamp (2005)
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132, 5249-5260
| Abstract »
| Full Text »
| PDF »
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- T. Maity, N. Fuse, and P. A. Beachy (2005)
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102, 17026-17031
| Abstract »
| Full Text »
| PDF »
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- E. M. Rogers, C. A. Brennan, N. T. Mortimer, S. Cook, A. R. Morris, and K. Moses (2005)
Development
132, 4833-4843
| Abstract »
| Full Text »
| PDF »
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- M. Hu and R. A. Shivdasani (2005)
Cancer Res.
65, 8715-8722
| Abstract »
| Full Text »
| PDF »
- The function and expansion of the Patched- and Hedgehog-related homologs in C. elegans.
- O. Zugasti, J. Rajan, and P. E. Kuwabara (2005)
Genome Res.
15, 1402-1410
| Abstract »
| Full Text »
| PDF »
- Fordyce granules and hereditary non-polyposis colorectal cancer syndrome.
- C De Felice, S Parrini, G Chitano, M Gentile, L Dipaola, and G Latini (2005)
Gut
54, 1279-1282
| Abstract »
| Full Text »
| PDF »
- Mice Deficient in the Fused Homolog Do Not Exhibit Phenotypes Indicative of Perturbed Hedgehog Signaling during Embryonic Development.
- M.-H. Chen, N. Gao, T. Kawakami, and P.-T. Chuang (2005)
Mol. Cell. Biol.
25, 7042-7053
| Abstract »
| Full Text »
| PDF »
- A previously unidentified amino-terminal domain regulates transcriptional activity of wild-type and disease-associated human GLI2.
- E. Roessler, A. N. Ermilov, D. K. Grange, A. Wang, M. Grachtchouk, A. A. Dlugosz, and M. Muenke (2005)
Hum. Mol. Genet.
14, 2181-2188
| Abstract »
| Full Text »
| PDF »
- Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors.
- A. Liu, B. Wang, and L. A. Niswander (2005)
Development
132, 3103-3111
| Abstract »
| Full Text »
| PDF »
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- F. Charron and M. Tessier-Lavigne (2005)
Development
132, 2251-2262
| Abstract »
| Full Text »
| PDF »
- Therapeutic Targeting of the Hedgehog-GLI Pathway in Prostate Cancer.
- P. Sanchez, V. Clement, and A. Ruiz i Altaba (2005)
Cancer Res.
65, 2990-2992
| Abstract »
| Full Text »
| PDF »
- Differential regulation of Hedgehog target gene transcription by Costal2 and Suppressor of Fused.
- K. S. Ho, K. Suyama, M. Fish, and M. P. Scott (2005)
Development
132, 1401-1412
| Abstract »
| Full Text »
| PDF »
- Profiling early infection responses: Pseudomonas aeruginosa eludes host defenses by suppressing antimicrobial peptide gene expression.
- Y. Apidianakis, M. N. Mindrinos, W. Xiao, G. W. Lau, R. L. Baldini, R. W. Davis, and L. G. Rahme (2005)
PNAS
102, 2573-2578
| Abstract »
| Full Text »
| PDF »
- A homologue of the Drosophila kinesin-like protein Costal2 regulates Hedgehog signal transduction in the vertebrate embryo.
- S. Y. Tay, P. W. Ingham, and S. Roy (2005)
Development
132, 625-634
| Abstract »
| Full Text »
| PDF »
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- C. Zhang, E. H. Williams, Y. Guo, L. Lum, and P. A. Beachy (2004)
PNAS
101, 17900-17907
| Abstract »
| Full Text »
| PDF »
- An Intramolecular Association between Two Domains of the Protein Kinase Fused Is Necessary for Hedgehog Signaling.
- M. Ascano Jr. and D. J. Robbins (2004)
Mol. Cell. Biol.
24, 10397-10405
| Abstract »
| Full Text »
| PDF »
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- A. I. Ivanov, A. C. Rovescalli, P. Pozzi, S. Yoo, B. Mozer, H.-P. Li, S.-H. Yu, H. Higashida, V. Guo, M. Spencer, et al. (2004)
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| Abstract »
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