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dc.contributor.authorPettigrew, Christopher A.
dc.contributor.authorAsp, Eva
dc.contributor.authorEmerson, Charles P. Jr.
dc.date2022-08-11T08:11:04.000
dc.date.accessioned2022-08-23T17:30:46Z
dc.date.available2022-08-23T17:30:46Z
dc.date.issued2014-02-01
dc.date.submitted2022-05-19
dc.identifier.citation<p>Pettigrew CA, Asp E, Emerson CP Jr. A new role for Hedgehogs in juxtacrine signaling. Mech Dev. 2014 Feb;131:137-49. doi: 10.1016/j.mod.2013.12.002. Epub 2013 Dec 14. PMID: 24342078; PMCID: PMC4220416. <a href="https://doi.org/10.1016/j.mod.2013.12.002">Link to article on publisher's site</a></p>
dc.identifier.issn0925-4773 (Linking)
dc.identifier.doi10.1016/j.mod.2013.12.002
dc.identifier.pmid24342078
dc.identifier.urihttp://hdl.handle.net/20.500.14038/50583
dc.description.abstractThe Hedgehog pathway plays important roles in embryonic development, adult stem cell maintenance and tumorigenesis. In mammals these effects are mediated by Sonic, Desert and Indian Hedgehog (Shh, Dhh and Ihh). Shh undergoes autocatalytic cleavage and dual lipidation prior to secretion and forming a response gradient. Post-translational processing and secretion of Dhh and Ihh ligands has not previously been investigated. This study reports on the synthesis, processing, secretion and signaling activities of SHH, IHH and DHH preproteins expressed in cultured cells, providing unexpected evidence that DHH does not undergo substantial autoprocessing or secretion, and does not function in paracrine signaling. Rather, DHH functions as a juxtacrine signaling ligand to activate a cell contact-mediated HH signaling response, consistent with its localised signaling in vivo. Further, the LnCAP prostate cancer cell, when induced to express endogenous DHH and SHH, is active only in juxtacrine signaling. Domain swap studies reveal that the C-terminal domain of HH regulates its processing and secretion. These findings establish a new regulatory role for HHs in cell-mediated juxtacrine signaling in development and cancer.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24342078&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1016/j.mod.2013.12.002
dc.subjectDevelopment
dc.subjectHedgehog
dc.subjectProcessing
dc.subjectSecretion
dc.subjectSignaling
dc.subjectCancer Biology
dc.subjectCell Biology
dc.subjectDevelopmental Biology
dc.titleA new role for Hedgehogs in juxtacrine signaling
dc.typeJournal Article
dc.source.journaltitleMechanisms of development
dc.source.volume131
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/wellstone_pubs/51
dc.identifier.contextkey29258868
html.description.abstract<p>The Hedgehog pathway plays important roles in embryonic development, adult stem cell maintenance and tumorigenesis. In mammals these effects are mediated by Sonic, Desert and Indian Hedgehog (Shh, Dhh and Ihh). Shh undergoes autocatalytic cleavage and dual lipidation prior to secretion and forming a response gradient. Post-translational processing and secretion of Dhh and Ihh ligands has not previously been investigated. This study reports on the synthesis, processing, secretion and signaling activities of SHH, IHH and DHH preproteins expressed in cultured cells, providing unexpected evidence that DHH does not undergo substantial autoprocessing or secretion, and does not function in paracrine signaling. Rather, DHH functions as a juxtacrine signaling ligand to activate a cell contact-mediated HH signaling response, consistent with its localised signaling in vivo. Further, the LnCAP prostate cancer cell, when induced to express endogenous DHH and SHH, is active only in juxtacrine signaling. Domain swap studies reveal that the C-terminal domain of HH regulates its processing and secretion. These findings establish a new regulatory role for HHs in cell-mediated juxtacrine signaling in development and cancer.</p>
dc.identifier.submissionpathwellstone_pubs/51
dc.contributor.departmentEmerson Lab
dc.contributor.departmentWellstone Muscular Dystrophy Program
dc.contributor.departmentDepartment of Neurology
dc.source.pages137-49


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