Smoothened

Smoothened

Smoothened is a G protein-coupled receptorcite journal | author = Ruiz-Gómez A, Molnar C, Holguín H, Mayor F, de Celis JF | title = The cell biology of Smo signalling and its relationships with GPCRs | journal = Biochim. Biophys. Acta | volume = 1768 | issue = 4 | pages = 901–12 | year = 2007 | pmid = 17094938 | doi = 10.1016/j.bbamem.2006.09.020 | issn = ] protein encoded by the gene|SMO gene of the hedgehog pathway conserved from flies to humans. It is the molecular target of the teratogen cyclopamine.cite journal | author = Taipale J, Chen JK, Cooper MK, Wang B, Mann RK, Milenkovic L, Scott MP, Beachy PA | title = Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine | journal = Nature | volume = 406 | issue = 6799 | pages = 1005–9 | year = 2000 | pmid = 10984056 | doi = 10.1038/35023008 | issn = ]

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.cite journal | author = Corbit KC, Aanstad P, Singla V, Norman AR, Stainier DY, Reiter JF | title = Vertebrate Smoothened functions at the primary cilium | journal = Nature | volume = 437 | issue = 7061 | pages = 1018–21 | year = 2005 | pmid = 16136078 | doi = 10.1038/nature04117 | issn = ] 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.cite journal | author = Lum L, Zhang C, Oh S, Mann RK, von Kessler DP, Taipale J, Weis-Garcia F, Gong R, Wang B, Beachy PA | title = Hedgehog signal transduction via Smoothened association with a cytoplasmic complex scaffolded by the atypical kinesin, Costal-2 | journal = Mol. Cell | volume = 12 | issue = 5 | pages = 1261–74 | year = 2003 | month = November | pmid = 14636583 | doi = 10.1016/S1097-2765(03)00426-X | issn = ]

SMO can function as an oncogene. Activating SMO mutations can lead to unregulated activation of the hedgehog pathway and cancer.cite journal | author = 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 | title = Activating Smoothened mutations in sporadic basal-cell carcinoma | journal = Nature | volume = 391 | issue = 6662 | pages = 90–2 | year = 1998 | pmid = 9422511 | doi = 10.1038/34201 | issn = ]

ee also

* Frizzled

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Chen Y, Struhl G |title=Dual roles for patched in sequestering and transducing Hedgehog. |journal=Cell |volume=87 |issue= 3 |pages= 553–63 |year= 1996 |pmid= 8898207 |doi=
*cite journal | author=Stone DM, Hynes M, Armanini M, "et al." |title=The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. |journal=Nature |volume=384 |issue= 6605 |pages= 129–34 |year= 1996 |pmid= 8906787 |doi= 10.1038/384129a0
*cite journal | author=Xie J, Murone M, Luoh SM, "et al." |title=Activating Smoothened mutations in sporadic basal-cell carcinoma. |journal=Nature |volume=391 |issue= 6662 |pages= 90–2 |year= 1998 |pmid= 9422511 |doi= 10.1038/34201
*cite journal | author=Reifenberger J, Wolter M, Weber RG, "et al." |title=Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. |journal=Cancer Res. |volume=58 |issue= 9 |pages= 1798–803 |year= 1998 |pmid= 9581815 |doi=
*cite journal | author=Sublett JE, Entrekin RE, Look AT, Reardon DA |title=Chromosomal localization of the human smoothened gene (SMOH) to 7q32. 3 by fluorescence in situ hybridization and radiation hybrid mapping. |journal=Genomics |volume=50 |issue= 1 |pages= 112–4 |year= 1999 |pmid= 9628830 |doi= 10.1006/geno.1998.5227
*cite journal | author=McGarvey TW, Maruta Y, Tomaszewski JE, "et al." |title=PTCH gene mutations in invasive transitional cell carcinoma of the bladder. |journal=Oncogene |volume=17 |issue= 9 |pages= 1167–72 |year= 1998 |pmid= 9764827 |doi= 10.1038/sj.onc.1202045
*cite journal | author=Chidambaram A, Gerrard B, Hanson M, Dean M |title=Chromosomal localization of the human and murine orthologues of the Drosophila smoothened gene. |journal=Genomics |volume=53 |issue= 3 |pages= 416–7 |year= 1998 |pmid= 9799615 |doi= 10.1006/geno.1998.5531
*cite journal | author=Carpenter D, Stone DM, Brush J, "et al." |title=Characterization of two patched receptors for the vertebrate hedgehog protein family. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 23 |pages= 13630–4 |year= 1998 |pmid= 9811851 |doi=
*cite journal | author=Detmer K, Walker AN, Jenkins TM, "et al." |title=Erythroid differentiation in vitro is blocked by cyclopamine, an inhibitor of hedgehog signaling. |journal=Blood Cells Mol. Dis. |volume=26 |issue= 4 |pages= 360–72 |year= 2000 |pmid= 11042037 |doi= 10.1006/bcmd.2000.0318
*cite journal | author=Long F, Zhang XM, Karp S, "et al." |title=Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation. |journal=Development |volume=128 |issue= 24 |pages= 5099–108 |year= 2002 |pmid= 11748145 |doi=
*cite journal | author=Incardona JP, Gruenberg J, Roelink H |title=Sonic hedgehog induces the segregation of patched and smoothened in endosomes. |journal=Curr. Biol. |volume=12 |issue= 12 |pages= 983–95 |year= 2002 |pmid= 12123571 |doi=
*cite journal | author=Lowrey JA, Stewart GA, Lindey S, "et al." |title=Sonic hedgehog promotes cell cycle progression in activated peripheral CD4(+) T lymphocytes. |journal=J. Immunol. |volume=169 |issue= 4 |pages= 1869–75 |year= 2002 |pmid= 12165511 |doi=
*cite journal | author=Taipale J, Cooper MK, Maiti T, Beachy PA |title=Patched acts catalytically to suppress the activity of Smoothened. |journal=Nature |volume=418 |issue= 6900 |pages= 892–7 |year= 2002 |pmid= 12192414 |doi= 10.1038/nature00989
*cite journal | author=Katayam M, Yoshida K, Ishimori H, "et al." |title=Patched and smoothened mRNA expression in human astrocytic tumors inversely correlates with histological malignancy. |journal=J. Neurooncol. |volume=59 |issue= 2 |pages= 107–15 |year= 2003 |pmid= 12241103 |doi=
*cite journal | author=Strausberg RL, Feingold EA, Grouse LH, "et al." |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899
*cite journal | author=Couvé-Privat S, Bouadjar B, Avril MF, "et al." |title=Significantly high levels of ultraviolet-specific mutations in the smoothened gene in basal cell carcinomas from DNA repair-deficient xeroderma pigmentosum patients. |journal=Cancer Res. |volume=62 |issue= 24 |pages= 7186–9 |year= 2003 |pmid= 12499255 |doi=
*cite journal | author=Scherer SW, Cheung J, MacDonald JR, "et al." |title=Human chromosome 7: DNA sequence and biology. |journal=Science |volume=300 |issue= 5620 |pages= 767–72 |year= 2003 |pmid= 12690205 |doi= 10.1126/science.1083423
*cite journal | author=Grachtchouk V, Grachtchouk M, Lowe L, "et al." |title=The magnitude of hedgehog signaling activity defines skin tumor phenotype. |journal=EMBO J. |volume=22 |issue= 11 |pages= 2741–51 |year= 2003 |pmid= 12773389 |doi= 10.1093/emboj/cdg271
*cite journal | author=Gerhard DS, Wagner L, Feingold EA, "et al." |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504
*cite journal | author=Chen W, Ren XR, Nelson CD, "et al." |title=Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2. |journal=Science |volume=306 |issue= 5705 |pages= 2257–60 |year= 2005 |pmid= 15618519 |doi= 10.1126/science.1104135

External links

* [http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3069 IUPHAR GPCR Database - Smoothened receptor]
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