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Pathway Description
Sonic Hedgehog Signaling
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Signaling
Created: 2025-02-09
Last Updated: 2025-04-22
Hedgehog (Hh) signaling plays a crucial role in vertebrate development by facilitating intracellular communication. The activation of Sonic Hedgehog (Shh) signaling occurs through a ligand-dependent interaction, where Shh binds to the Patched (Ptch) receptor on the cell membrane of the receiving cell. Upon Shh binding, Ptch is no longer able to inhibit Smoothened (Smo), allowing Smo to accumulate in the cilium. This accumulation leads to the activation of Smo, which in turn triggers a signaling cascade that affects the processing of Gli transcription factors. Smo activates the protein complex containing Gli, Sudu, and Kif7. Gli proteins, which are key mediators of the pathway, are translocated into the nucleus, where they regulate the expression of target genes.
References
Sonic Hedgehog Signaling References
Carballo, G.B., Honorato, J.R., de Lopes, G.P. et al. A highlight on Sonic hedgehog pathway. Cell Commun Signal 16, 11 (2018). https://doi.org/10.1186/s12964-018-0220-7
Briscoe, J., Thérond, P. The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol 14, 416–429 (2013). https://doi.org/10.1038/nrm3598
Heretsch, P., Tzagkaroulaki, L., & Giannis, A. (2010). Modulators of the hedgehog signaling pathway. Bioorganic & Medicinal Chemistry, 18(18), 6613–6624. https://doi.org/10.1016/j.bmc.2010.07.038
Marigo V, Roberts DJ, Lee SM, Tsukurov O, Levi T, Gastier JM, Epstein DJ, Gilbert DJ, Copeland NG, Seidman CE, et al.: Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog. Genomics. 1995 Jul 1;28(1):44-51.
Pubmed: 7590746
Sun M, Ma F, Zeng X, Liu Q, Zhao XL, Wu FX, Wu GP, Zhang ZF, Gu B, Zhao YF, Tian SH, Lin B, Kong XY, Zhang XL, Yang W, Lo WH, Zhang X: Triphalangeal thumb-polysyndactyly syndrome and syndactyly type IV are caused by genomic duplications involving the long range, limb-specific SHH enhancer. J Med Genet. 2008 Sep;45(9):589-95. doi: 10.1136/jmg.2008.057646. Epub 2008 Apr 16.
Pubmed: 18417549
Wieczorek D, Pawlik B, Li Y, Akarsu NA, Caliebe A, May KJ, Schweiger B, Vargas FR, Balci S, Gillessen-Kaesbach G, Wollnik B: A specific mutation in the distant sonic hedgehog (SHH) cis-regulator (ZRS) causes Werner mesomelic syndrome (WMS) while complete ZRS duplications underlie Haas type polysyndactyly and preaxial polydactyly (PPD) with or without triphalangeal thumb. Hum Mutat. 2010 Jan;31(1):81-9. doi: 10.1002/humu.21142.
Pubmed: 19847792
Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH Jr, Scott MP: Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science. 1996 Jun 14;272(5268):1668-71. doi: 10.1126/science.272.5268.1668.
Pubmed: 8658145
Hahn H, Christiansen J, Wicking C, Zaphiropoulos PG, Chidambaram A, Gerrard B, Vorechovsky I, Bale AE, Toftgard R, Dean M, Wainwright B: A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities. J Biol Chem. 1996 May 24;271(21):12125-8. doi: 10.1074/jbc.271.21.12125.
Pubmed: 8647801
Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. doi: 10.1038/nature02465.
Pubmed: 15164053
Sweeney RT, McClary AC, Myers BR, Biscocho J, Neahring L, Kwei KA, Qu K, Gong X, Ng T, Jones CD, Varma S, Odegaard JI, Sugiyama T, Koyota S, Rubin BP, Troxell ML, Pelham RJ, Zehnder JL, Beachy PA, Pollack JR, West RB: Identification of recurrent SMO and BRAF mutations in ameloblastomas. Nat Genet. 2014 Jul;46(7):722-5. doi: 10.1038/ng.2986. Epub 2014 May 25.
Pubmed: 24859340
Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL, Scott MP, Pennica D, Goddard A, Phillips H, Noll M, Hooper JE, de Sauvage F, Rosenthal A: The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature. 1996 Nov 14;384(6605):129-34. doi: 10.1038/384129a0.
Pubmed: 8906787
Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, Bonifas JM, Lam CW, Hynes M, Goddard A, Rosenthal A, Epstein EH Jr, de Sauvage FJ: Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature. 1998 Jan 1;391(6662):90-2. doi: 10.1038/34201.
Pubmed: 9422511
Kawakami Y, Wang X, Shofuda T, Sumimoto H, Tupesis J, Fitzgerald E, Rosenberg S: Isolation of a new melanoma antigen, MART-2, containing a mutated epitope recognized by autologous tumor-infiltrating T lymphocytes. J Immunol. 2001 Feb 15;166(4):2871-7. doi: 10.4049/jimmunol.166.4.2871.
Pubmed: 11160356
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. doi: 10.1186/1471-2164-8-399.
Pubmed: 17974005
Lo HW, Zhu H, Cao X, Aldrich A, Ali-Osman F: A novel splice variant of GLI1 that promotes glioblastoma cell migration and invasion. Cancer Res. 2009 Sep 1;69(17):6790-8. doi: 10.1158/0008-5472.CAN-09-0886. Epub 2009 Aug 25.
Pubmed: 19706761
Wang XQ, Chan N, Rothnagel JA: Letters to the editor: identification of polymorphic variants of the GLI1 oncogene. J Invest Dermatol. 2000 Aug;115(2):328-9. doi: 10.1046/j.1523-1747.2000.00065.x.
Pubmed: 10951255
Kinzler KW, Ruppert JM, Bigner SH, Vogelstein B: The GLI gene is a member of the Kruppel family of zinc finger proteins. Nature. 1988 Mar 24;332(6162):371-4. doi: 10.1038/332371a0.
Pubmed: 2832761
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