Smoothened
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Smoothened is a G protein-coupled receptor[1] protein encoded by the SMO gene of the hedgehog pathway conserved from flies to humans. It is the molecular target of the teratogen cyclopamine.[2]
Cellular localization plays an essential role in the function of SMO. Stimulation of the patched receptor by the sonic hedgehog ligand leads to translocation of SMO to the primary cilium. Furthermore, SMO that is mutated in the domain required for ciliary localisation cannot contribute to pathway activation.[3] SMO has also been shown to bind the kinesin motor protein Costal-2 and play a role in the localization of the Ci (Cubitus interruptus transcription factor) complex.[4]
SMO can function as an oncogene. Activating SMO mutations can lead to unregulated activation of the hedgehog pathway and cancer.[5]
File:Signal transduction v1.png
Overview of signal transduction pathways involved in apoptosis.
See also
References
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<references />, or <references group="..." />Further reading
- Chen Y, Struhl G (1996). "Dual roles for patched in sequestering and transducing Hedgehog". Cell. 87 (3): 553–63. doi:10.1016/S0092-8674(00)81374-4. PMID 8898207.
- Stone DM, Hynes M, Armanini M; et al. (1996). "The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog". Nature. 384 (6605): 129–34. doi:10.1038/384129a0. PMID 8906787.
- Xie J, Murone M, Luoh SM; et al. (1998). "Activating Smoothened mutations in sporadic basal-cell carcinoma". Nature. 391 (6662): 90–2. doi:10.1038/34201. PMID 9422511.
- Reifenberger J, Wolter M, Weber RG; et al. (1998). "Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system". Cancer Res. 58 (9): 1798–803. PMID 9581815.
- Sublett JE, Entrekin RE, Look AT, Reardon DA (1999). "Chromosomal localization of the human smoothened gene (SMOH) to 7q32. 3 by fluorescence in situ hybridization and radiation hybrid mapping". Genomics. 50 (1): 112–4. doi:10.1006/geno.1998.5227. PMID 9628830.
- McGarvey TW, Maruta Y, Tomaszewski JE; et al. (1998). "PTCH gene mutations in invasive transitional cell carcinoma of the bladder". Oncogene. 17 (9): 1167–72. doi:10.1038/sj.onc.1202045. PMID 9764827.
- Chidambaram A, Gerrard B, Hanson M, Dean M (1998). "Chromosomal localization of the human and murine orthologues of the Drosophila smoothened gene". Genomics. 53 (3): 416–7. doi:10.1006/geno.1998.5531. PMID 9799615.
- Carpenter D, Stone DM, Brush J; et al. (1998). "Characterization of two patched receptors for the vertebrate hedgehog protein family". Proc. Natl. Acad. Sci. U.S.A. 95 (23): 13630–4. doi:10.1073/pnas.95.23.13630. PMC 24870 Freely accessible. PMID 9811851.
- Detmer K, Walker AN, Jenkins TM; et al. (2000). "Erythroid differentiation in vitro is blocked by cyclopamine, an inhibitor of hedgehog signaling". Blood Cells Mol. Dis. 26 (4): 360–72. doi:10.1006/bcmd.2000.0318. PMID 11042037.
- Long F, Zhang XM, Karp S; et al. (2002). "Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation". Development. 128 (24): 5099–108. PMID 11748145.
- Incardona JP, Gruenberg J, Roelink H (2002). "Sonic hedgehog induces the segregation of patched and smoothened in endosomes". Curr. Biol. 12 (12): 983–95. doi:10.1016/S0960-9822(02)00895-3. PMID 12123571.
- Lowrey JA, Stewart GA, Lindey S; et al. (2002). "Sonic hedgehog promotes cell cycle progression in activated peripheral CD4(+) T lymphocytes". J. Immunol. 169 (4): 1869–75. PMID 12165511.
- Taipale J, Cooper MK, Maiti T, Beachy PA (2002). "Patched acts catalytically to suppress the activity of Smoothened". Nature. 418 (6900): 892–7. doi:10.1038/nature00989. PMID 12192414.
- Katayam M, Yoshida K, Ishimori H; et al. (2003). "Patched and smoothened mRNA expression in human astrocytic tumors inversely correlates with histological malignancy". J. Neurooncol. 59 (2): 107–15. doi:10.1023/A:1019660421216. PMID 12241103.
- Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241 Freely accessible. PMID 12477932.
- Couvé-Privat S, Bouadjar B, Avril MF; et al. (2003). "Significantly high levels of ultraviolet-specific mutations in the smoothened gene in basal cell carcinomas from DNA repair-deficient xeroderma pigmentosum patients". Cancer Res. 62 (24): 7186–9. PMID 12499255.
- Scherer SW, Cheung J, MacDonald JR; et al. (2003). "Human chromosome 7: DNA sequence and biology". Science. 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961 Freely accessible. PMID 12690205.
- Grachtchouk V, Grachtchouk M, Lowe L; et al. (2003). "The magnitude of hedgehog signaling activity defines skin tumor phenotype". EMBO J. 22 (11): 2741–51. doi:10.1093/emboj/cdg271. PMC 156767 Freely accessible. PMID 12773389.
- Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928 Freely accessible. PMID 15489334.
- Chen W, Ren XR, Nelson CD; et al. (2005). "Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2". Science. 306 (5705): 2257–60. doi:10.1126/science.1104135. PMID 15618519.
External links
- "Frizzled Receptors: SMO". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- MeSH SMO+protein,+human
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- ↑ Ruiz-Gómez A, Molnar C, Holguín H, Mayor F, de Celis JF (2007). "The cell biology of Smo signalling and its relationships with GPCRs". Biochim. Biophys. Acta. 1768 (4): 901–12. doi:10.1016/j.bbamem.2006.09.020. PMID 17094938.
- ↑ Taipale J, Chen JK, Cooper MK, Wang B, Mann RK, Milenkovic L, Scott MP, Beachy PA (2000). "Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine". Nature. 406 (6799): 1005–9. doi:10.1038/35023008. PMID 10984056.
- ↑ Corbit KC, Aanstad P, Singla V, Norman AR, Stainier DY, Reiter JF (2005). "Vertebrate Smoothened functions at the primary cilium". Nature. 437 (7061): 1018–21. doi:10.1038/nature04117. PMID 16136078.
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
- ↑ Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, Bonifas JM, Lam CW, Hynes M, Goddard A, Rosenthal A, Epstein EH, de Sauvage FJ (1998). "Activating Smoothened mutations in sporadic basal-cell carcinoma". Nature. 391 (6662): 90–2. doi:10.1038/34201. PMID 9422511.
