dc.contributor.author | El Jellas, Khadija | en_US |
dc.contributor.author | Johansson, Bente Berg | en_US |
dc.contributor.author | Fjeld, Karianne | en_US |
dc.contributor.author | Antonopoulos, Aristotelis | en_US |
dc.contributor.author | Immervoll, Heike | en_US |
dc.contributor.author | Choi, Man Hung | en_US |
dc.contributor.author | Hoem, Dag | en_US |
dc.contributor.author | Lowe, Mark E. | en_US |
dc.contributor.author | Lombardo, Dominique | en_US |
dc.contributor.author | Njølstad, Pål Rasmus | en_US |
dc.contributor.author | Dell, Anne | en_US |
dc.contributor.author | Mas, Eric | en_US |
dc.contributor.author | Haslam, Stuart M. | en_US |
dc.contributor.author | Molven, Anders | en_US |
dc.date.accessioned | 2019-02-21T13:10:29Z | |
dc.date.available | 2019-02-21T13:10:29Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 0021-9258 | |
dc.identifier.uri | https://hdl.handle.net/1956/19132 | |
dc.description.abstract | Carboxyl-ester lipase (CEL) is a pancreatic fat-digesting enzyme associated with human disease. Rare mutations in the CEL gene cause a syndrome of pancreatic exocrine and endocrine dysfunction denoted MODY8, whereas a recombined CEL allele increases the risk for chronic pancreatitis. Moreover, CEL has been linked to pancreatic ductal adenocarcinoma (PDAC) through a postulated oncofetal CEL variant termed feto-acinar pancreatic protein (FAPP). The monoclonal antibody mAb16D10 was previously reported to detect a glycotope in the highly O-glycosylated, mucin-like C terminus of CEL/FAPP. We here assessed the expression of human CEL in malignant pancreatic lesions and cell lines. CEL was not detectably expressed in neoplastic cells, implying that FAPP is unlikely to be a glycoisoform of CEL in pancreatic cancer. Testing of the mAb16D10 antibody in glycan microarrays then demonstrated that it recognized structures containing terminal GalNAc- 1,3(Fuc- 1,2)Gal (blood group A antigen) and also repeated protein sequences containing GalNAc residues linked to Ser/Thr (Tn antigen), findings that were supported by immunostainings of human pancreatic tissue. To examine whether the CEL glycoprotein might be modified by blood group antigens, we used high-sensitivity MALDI-TOF MS to characterize the released O-glycan pool ofCELimmunoprecipitatedfromhumanpancreatic juice. We found that the O-glycome of CEL consisted mainly of core 1/core 2 structures with a composition depending on the subject’s FUT2 and ABO gene polymorphisms. Thus, among digestive enzymes secreted by the pancreas,CELis a glycoprotein with some unique characteristics, supporting the view that it could serve additional biological functions to its cholesteryl esterase activity in the duodenum. | en_US |
dc.language.iso | eng | eng |
dc.publisher | The American Society for Biochemistry and Molecular Biology | eng |
dc.rights | This research was originally published in the Journal of Biological Chemistry. El Jellas et al. The mucinous domain of pancreatic carboxyl-ester lipase (CEL) contains core 1/core 2 O-glycans that can be modified by ABO blood group determinants. J. Biol. Chem. 2018; 293(50):19476-19491. © the Author(s). | eng |
dc.title | The mucinous domain of pancreatic carboxyl-ester lipase (CEL) contains core 1/core 2 O-glycans that can be modified by ABO blood group determinants | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2018 El Jellas et al. | |
dc.identifier.doi | https://doi.org/10.1074/jbc.ra118.001934 | |
dc.identifier.cristin | 1678800 | |
dc.source.journal | Journal of Biological Chemistry | |
dc.source.40 | 293 | |
dc.source.14 | 50 | |
dc.source.pagenumber | 19476-19491 | |
dc.identifier.citation | Journal of Biological Chemistry. 2018, 293 (50), 19476-19491. | |