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Although the Hh and Wnt proteins are unrelated, they are similar in that they carry lipid modifications that are critical for their interaction with their receptors. In our earlier work we have shown that Wnt inhibitory factor 1 (WIF1), originally identified as a Wnt antagonist also binds to and inhibits the signaling activity of sonic hedgehog (Shh), raising the possibility that the lipid moieties of these unrelated morphogens play a dominant role in their interaction with WIF1. In the present work we have compared the interactions of human WIF1 protein with lipidated and non-lipidated forms of human Shh using surface plasmon resonance spectroscopy and reporter assays monitoring the signaling activity of human Shh. Our studies have shown that human WIF1 protein has a modest but significantly higher affinity for lipidated than non-lipidated Shh, indicating that lipid modifications of Shh contribute to but are not essential for interaction with WIF1.<\/jats:p>","DOI":"10.1042\/bcj20260508","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:36:27Z","timestamp":1786977387000},"page":"1773-1783","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipid moieties of sonic hedgehog contribute to but are not essential for interaction with its inhibitor, WIF1"],"prefix":"10.1042","volume":"483","author":[{"given":"Krisztina","family":"Kerekes","sequence":"first","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1ria","family":"Trexler","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"B\u00e1nyai","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1329-0484","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Patthy","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"2026082503313190500_B1","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/S0962-8924(02)02388-7","article-title":"Similarities between the Hedgehog and Wnt signaling pathways","volume":"12","author":"Kalderon","year":"2002","journal-title":"Trends Cell Biol."},{"key":"2026082503313190500_B2","doi-asserted-by":"publisher","first-page":"5297","DOI":"10.1242\/dev.00821","article-title":"Wnts and Hedgehogs: lipid-modified proteins and similarities in signaling mechanisms at the cell surface","volume":"130","author":"Nusse","year":"2003","journal-title":"Development"},{"key":"2026082503313190500_B3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1080\/08977194.2019.1626380","article-title":"Structure, function and disease relevance of Wnt inhibitory factor 1, a secreted protein controlling the Wnt and hedgehog pathways","volume":"37","author":"Kerekes","year":"2019","journal-title":"Growth Factors"},{"key":"2026082503313190500_B4","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.devcel.2005.01.003","article-title":"Shifted, the Drosophila ortholog of Wnt inhibitory factor-1, controls the distribution and movement of Hedgehog","volume":"8","author":"Glise","year":"2005","journal-title":"Dev. 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