title: AGR2, an endoplasmic reticulum protein, is secreted into the gastrointestinal mucus.
abstract: The MUC2 mucin is the major constituent of the two mucus layers in colon. Mice lacking the disulfide isomerase-like protein Agr2 have been shown to be more susceptible to colon inflammation. The Agr2(-/-) mice have less filled goblet cells and were now shown to have a poorly developed inner colon mucus layer. We could not show AGR2 covalently bound to recombinant MUC2 N- and C-termini as have previously been suggested. We found relatively high concentrations of Agr2 in secreted mucus throughout the murine gastrointestinal tract, suggesting that Agr2 may play extracellular roles. In tissue culture (CHO-K1) cells, AGR2 is normally not secreted. Replacement of the single Cys in AGR2 with Ser (C81S) allowed secretion, suggesting that modification of this Cys might provide a mechanism for circumventing the KTEL endoplasmic reticulum retention signal. In conclusion, these results suggest that AGR2 has both intracellular and extracellular effects in the intestine.
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Joakim H
authors.initials: JH
authors.lastname: Bergström
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Katarina A
authors.initials: KA
authors.lastname: Berg
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rodríguez-Piñeiro
authors.affiliation: Max von Pettenkofer Institute for Hygiene and Medical Microbiology, LMU Munich, Munich, Germany.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Stecher
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Malin E V
authors.initials: ME
authors.lastname: Johansson
authors.affiliation: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Gunnar C
authors.initials: GC
authors.lastname: Hansson
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism*; D008297:Male; D051379:Mice; D009088:Mucoproteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009093:Mucus / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D015513:Oncogene Proteins; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C502296:AGR2 protein, human; C526445:Agr2 protein, mouse; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins
references.citation: J Biol Chem. 2012 Feb 10;287(7):4773-82
references.pmid: 22184114
references.citation: Science. 2002 Mar 1;295(5560):1726-9
references.pmid: 11872843
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15064-9
references.pmid: 18806221
references.citation: J Biol Chem. 2011 Dec 30;286(52):44855-68
references.pmid: 22025610
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13588-93
references.pmid: 21825124
references.citation: J Mol Biol. 2013 Mar 11;425(5):929-43
references.pmid: 23274113
references.citation: J Biol Chem. 2002 Dec 6;277(49):47248-56
references.pmid: 12374796
references.citation: Am J Physiol Gastrointest Liver Physiol. 2013 Sep 1;305(5):G341-7
references.pmid: 23832518
references.citation: J Biol Chem. 2013 Feb 8;288(6):4321-33
references.pmid: 23209296
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16209-14
references.pmid: 17911254
references.citation: J Biol Chem. 1999 Nov 5;274(45):31751-4
references.pmid: 10542193
references.citation: Biochem Biophys Res Commun. 2013 Jan 11;430(2):610-5
references.pmid: 23220234
references.citation: Nature. 1970 Aug 15;227(5259):680-5
references.pmid: 5432063
references.citation: J Proteome Res. 2009 Jul;8(7):3549-57
references.pmid: 19432394
references.citation: Biochem J. 2003 Jun 1;372(Pt 2):335-45
references.pmid: 12597771
references.citation: Gut. 2014 Feb;63(2):281-91
references.pmid: 23426893
references.citation: PLoS One. 2010 Aug 18;5(8):e12238
references.pmid: 20805871
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):6950-5
references.pmid: 19359471
references.citation: Biochem Biophys Res Commun. 1994 Jan 14;198(1):181-90
references.pmid: 8292021
references.citation: Oncogene. 2013 May 16;32(20):2499-509
references.pmid: 22945652
references.citation: Nat Rev Gastroenterol Hepatol. 2013 Jun;10(6):352-61
references.pmid: 23478383
references.citation: Dev Biol. 2012 Sep 15;369(2):249-60
references.pmid: 22819674
references.citation: Dev Biol. 2010 Feb 15;338(2):270-9
references.pmid: 20025862
references.citation: Genes Immun. 2006 Jan;7(1):11-8
references.pmid: 16222343
references.citation: Am J Physiol Gastrointest Liver Physiol. 2013 Sep 1;305(5):G348-56
references.pmid: 23832517
references.citation: J Biol Chem. 2011 May 20;286(20):18301-10
references.pmid: 21454516
references.citation: Am J Physiol Gastrointest Liver Physiol. 2012 Feb 15;302(4):G430-8
references.pmid: 22159279
references.citation: Development. 1996 Sep;122(9):2739-50
references.pmid: 8787748