Hedgehog signaling pathway
From Proteopedia
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'''Protein patched homolog 1''' (Ptch1) acts as receptor of [[Sonic Hedgehog]] protein (Shh) which is involved in formation of embryonic structures <ref>PMID:11001584</ref>. Embryogenesis is regulated by several pathways one of which is the Shh-Patch1-Gli all of which are highly conserved. | '''Protein patched homolog 1''' (Ptch1) acts as receptor of [[Sonic Hedgehog]] protein (Shh) which is involved in formation of embryonic structures <ref>PMID:11001584</ref>. Embryogenesis is regulated by several pathways one of which is the Shh-Patch1-Gli all of which are highly conserved. | ||
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| - | == Disease == | ||
Mutations in Ptch1 are associated with holoprosencephaly<ref>PMID:11941477</ref>. | Mutations in Ptch1 are associated with holoprosencephaly<ref>PMID:11941477</ref>. | ||
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| - | ==Relevance == | ||
High expression of Ptch1 messenger RNA indicates a risk of postresection recurrence of hepatocellular carcinoma<ref>PMID:22911366</ref>. | High expression of Ptch1 messenger RNA indicates a risk of postresection recurrence of hepatocellular carcinoma<ref>PMID:22911366</ref>. | ||
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| - | == Structural highlights == | ||
<scene name='87/874449/Cv/7'>The complex between Ptch1 and Shh</scene>. Ptch1 <scene name='87/874449/Cv/6'>consists of ectodomain 1 (residues 139-428) and ectodomain 2</scene> (residues 772-1023). <scene name='87/874449/Cv/8'>All Ptch1/Shh interactions</scene>. Ptch1 ectodomain 1 (colored in salmon) interacts with Shh as well as Ptch1 ectodomain 2 (colored in wheat) with <scene name='87/874449/Cv/10'>multiple acidic residues of Ptch1 (in crimson) interacting with the Lys/Arg patch of Shh (in royalblue)</scene>. The Ptch1-Shh interaction is steroid-dependent and the 3D structure shows <scene name='87/874449/Cv/12'>the location of cholesterol hemisuccinate between ectodomains 1 and 2 of Ptch1</scene><ref>PMID:31127104</ref>. | <scene name='87/874449/Cv/7'>The complex between Ptch1 and Shh</scene>. Ptch1 <scene name='87/874449/Cv/6'>consists of ectodomain 1 (residues 139-428) and ectodomain 2</scene> (residues 772-1023). <scene name='87/874449/Cv/8'>All Ptch1/Shh interactions</scene>. Ptch1 ectodomain 1 (colored in salmon) interacts with Shh as well as Ptch1 ectodomain 2 (colored in wheat) with <scene name='87/874449/Cv/10'>multiple acidic residues of Ptch1 (in crimson) interacting with the Lys/Arg patch of Shh (in royalblue)</scene>. The Ptch1-Shh interaction is steroid-dependent and the 3D structure shows <scene name='87/874449/Cv/12'>the location of cholesterol hemisuccinate between ectodomains 1 and 2 of Ptch1</scene><ref>PMID:31127104</ref>. | ||
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References
- ↑ Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J, McMahon JA, McMahon AP. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell. 1993 Dec 31;75(7):1417-30. PMID:7916661
- ↑ Villavicencio EH, Walterhouse DO, Iannaccone PM. The sonic hedgehog-patched-gli pathway in human development and disease. Am J Hum Genet. 2000 Nov;67(5):1047-54. doi: 10.1016/S0002-9297(07)62934-6. Epub , 2000 Sep 21. PMID:11001584 doi:http://dx.doi.org/10.1016/S0002-9297(07)62934-6
- ↑ Ming JE, Kaupas ME, Roessler E, Brunner HG, Golabi M, Tekin M, Stratton RF, Sujansky E, Bale SJ, Muenke M. Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly. Hum Genet. 2002 Apr;110(4):297-301. doi: 10.1007/s00439-002-0695-5. Epub 2002 Mar, 2. PMID:11941477 doi:http://dx.doi.org/10.1007/s00439-002-0695-5
- ↑ Jeng KS, Sheen IS, Jeng WJ, Lin CC, Lin CK, Su JC, Yu MC, Fang HY. High expression of patched homolog-1 messenger RNA and glioma-associated oncogene-1 messenger RNA of sonic hedgehog signaling pathway indicates a risk of postresection recurrence of hepatocellular carcinoma. Ann Surg Oncol. 2013 Feb;20(2):464-73. doi: 10.1245/s10434-012-2593-y. Epub 2012 , Aug 22. PMID:22911366 doi:http://dx.doi.org/10.1245/s10434-012-2593-y
- ↑ Qian H, Cao P, Hu M, Gao S, Yan N, Gong X. Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm. Nat Commun. 2019 May 24;10(1):2320. doi: 10.1038/s41467-019-10234-9. PMID:31127104 doi:http://dx.doi.org/10.1038/s41467-019-10234-9
