Human Intestinal TFF3 Forms Disulfide-Linked Heteromers with the Mucus-Associated FCGBP Protein and Is Released by Hydrogen Sulfide

被引:101
作者
Albert, Timo K. [1 ]
Laubinger, Werner [1 ]
Mueller, Stefan [2 ]
Hanisch, Franz-Georg [2 ]
Kalinski, Thomas [3 ]
Meyer, Frank [4 ]
Hoffmann, Werner [1 ]
机构
[1] Otto von Guericke Univ, Inst Mol Biol & Med Chem, D-39120 Magdeburg, Germany
[2] Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany
[3] Otto von Guericke Univ, Inst Pathol, D-39120 Magdeburg, Germany
[4] Otto von Guericke Univ, Dept Surg, D-39120 Magdeburg, Germany
关键词
TFF3; trefoil factor; IgGFc binding protein; mucin; hydrogen sulfide; restitution; mucosal repair; mucus; MUC2; CLCA1; EPIDERMAL-GROWTH-FACTOR; ADENOMA-CARCINOMA SEQUENCE; RAT COAGULATING GLAND; HUMAN GASTRIC-MUCOSA; TREFOIL FACTOR TFF3; XENOPUS-LAEVIS; DIFFERENTIAL EXPRESSION; BINDING-PROTEIN; GENETIC-POLYMORPHISM; INTEGUMENTARY MUCIN;
D O I
10.1021/pr100020c
中图分类号
Q5 [生物化学];
学科分类号
070307 [化学生物学];
摘要
TFF3 is a secretory peptide belonging to the trefoil factor family with a predicted size of 59 amino acid residues containing seven cysteine residues. It is predominantly expressed in intestinal goblet cells where it plays a key role in mucosal regeneration and repair processes. In the course of these studies, human colonic TFF3 was shown to exist mainly as a high molecular weight heteromer. Purification of this heteromer and characterization by LC-ESI-MS/MS analysis identified the IgG Fc binding protein (FCGBP) as the disulfide-linked partner protein of TFF3. FCGBP is a constituent of intestinal mucus secreted by goblet cells. Furthermore, low amounts of TFF3/monomer and only little TFF3/dimer were detected in human colonic extracts. Here, we show that these TFF3 forms can be released from the purified TFF3-FCGBP heteromer complex in vitro by reduction with hydrogen sulfide (H(2)S). Such a mechanism would be in line with the high H(2)S concentrations reported to occur in the lumen of the colon. Of special note, this points to intestinal mucus as a reservoir for a biologically active peptide. Also proteolytic processing of FCGBP was observed which is in line with multiple autocatalytic cleavages as proposed earlier by Johansson et al. (J. Proteome Res. 2009, 8, 3549-3557).
引用
收藏
页码:3108 / 3117
页数:10
相关论文
共 79 条
[1]
Apocrine secretion -: Fact or artifact? [J].
Aumüller, G ;
Wilhelm, B ;
Seitz, J .
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 1999, 181 (05) :437-446
[2]
IMPROVED SILVER STAINING OF PLANT-PROTEINS, RNA AND DNA IN POLYACRYLAMIDE GELS [J].
BLUM, H ;
BEIER, H ;
GROSS, HJ .
ELECTROPHORESIS, 1987, 8 (02) :93-99
[3]
CHARACTERIZATION OF THE SINGLE-COPY TREFOIL PEPTIDES INTESTINAL TREFOIL FACTOR AND PS2 AND THEIR ABILITY TO FORM COVALENT DIMERS [J].
CHINERY, R ;
BATES, PA ;
DE, A ;
FREEMONT, PS .
FEBS LETTERS, 1995, 357 (01) :50-54
[4]
Epidermal growth factor and trefoil factor family 2 synergistically trigger chemotaxis on BEAS-2B cells via different signaling cascades [J].
Chwieralski, CE ;
Schnurra, I ;
Thim, L ;
Hoffmann, W .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2004, 31 (05) :528-537
[5]
Protein kinase C and ERK activation are required for TFF-peptide-stimulated bronchial epithelial cell migration and tumor necrosis factor-α-induced interleukin-6 (IL-6) and IL-8 secretion [J].
Graness, A ;
Chwieralski, CE ;
Reinhold, D ;
Thim, L ;
Hoffmann, W .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (21) :18440-18446
[6]
Simultaneous apocrine and merocrine secretion in the rat coagulating gland [J].
Groos, S ;
Wilhelm, B ;
Renneberg, H ;
Riva, A ;
Reichelt, R ;
Seitz, J ;
Aumüller, G .
CELL AND TISSUE RESEARCH, 1999, 295 (03) :495-504
[7]
Genomic cloning, molecular characterization, and functional analysis of human CLCA1, the first human member of the family of Ca2+-activated Cl- channel proteins [J].
Gruber, AD ;
Elble, RC ;
Ji, HL ;
Schreur, KD ;
Fuller, CM ;
Pauli, BU .
GENOMICS, 1998, 54 (02) :200-214
[8]
Human IgGFc binding protein (Fc gamma BP) in colonic epithelial cells exhibits mucin-like structure [J].
Harada, N ;
Iijima, S ;
Kobayashi, K ;
Yoshida, T ;
Brown, WR ;
Hibi, T ;
Oshima, A ;
Morikawa, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (24) :15232-15241
[9]
HAUSER F, 1992, J BIOL CHEM, V267, P24620
[10]
HP1.B, A HUMAN P-DOMAIN PEPTIDE HOMOLOGOUS WITH RAT INTESTINAL TREFOIL FACTOR, IS EXPRESSED ALSO IN THE ULCER-ASSOCIATED CELL LINEAGE AND THE UTERUS [J].
HAUSER, F ;
POULSOM, R ;
CHINERY, R ;
ROGERS, LA ;
HANBY, AM ;
WRIGHT, NA ;
HOFFMANN, W .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (15) :6961-6965