Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Biochem J
2003 May 15;372Pt 1:263-70. doi: 10.1042/BJ20021333.
Show Gene links
Show Anatomy links
SEA (sea-urchin sperm protein, enterokinase and agrin)-module cleavage, association of fragments and membrane targeting of rat intestinal mucin Muc3.
Khatri IA
,
Wang R
,
Forstner JF
.
???displayArticle.abstract???
In a previous study we showed, by transient expression studies in COS-1 cells, that the C-terminal domain of rat intestinal membrane mucin Muc3 was cleaved between glycine and serine within a GSIVV (one-letter) amino acid sequence during its residence in the endoplasmic reticulum. The extracellular domain fragment remained linked to the membrane-associated fragment by non-covalent interactions. The present study demonstrates that cleavage depends not only on the presence of the G/SIVV site (where G/S is the glycine downward arrow serine cleavage site), but also on more distant C-terminal sequences in the SEA (sea-urchin sperm protein, enterokinase and agrin) module. Inhibition of N-glycosylation by tunicamycin treatment of transfected cells did not prevent re-association of fragments, although cleavage was partially impaired, as some of the non-glycosylated, non-cleaved products were seen to accumulate in cells. Membrane targeting of the Muc3 domain and its cleavage products occurred in transfected cells and was not impaired in mutants in which the cleavage site was mutated. Targeting was also not impaired for products devoid of N-linked oligosaccharides. Our studies thus indicate that (a) cleavage within the SEA module of rat Muc3 requires participation of peptide sequences located C-terminal of and distant from the cleavage site, (b) re-association of the fragments requires the SEA module, but is independent of N-linked oligosaccharides, and (c) membrane targeting of the mucin is independent of the SEA-module-cleavage reaction.
Abe,
Cleavage of Ig-Hepta at a "SEA" module and at a conserved G protein-coupled receptor proteolytic site.
2002, Pubmed
Abe,
Cleavage of Ig-Hepta at a "SEA" module and at a conserved G protein-coupled receptor proteolytic site.
2002,
Pubmed
Baruch,
The breast cancer-associated MUC1 gene generates both a receptor and its cognate binding protein.
1999,
Pubmed
Bork,
The SEA module: a new extracellular domain associated with O-glycosylation.
1995,
Pubmed
,
Echinobase
Buisine,
Mucin gene expression in intestinal epithelial cells in Crohn's disease.
2001,
Pubmed
Carraway,
Cell signaling through membrane mucins.
2003,
Pubmed
Carraway,
An intramembrane modulator of the ErbB2 receptor tyrosine kinase that potentiates neuregulin signaling.
1999,
Pubmed
Carraway,
Multiple facets of sialomucin complex/MUC4, a membrane mucin and erbb2 ligand, in tumors and tissues (Y2K update).
2000,
Pubmed
Gum,
MUC17, a novel membrane-tethered mucin.
2002,
Pubmed
Hanisch,
MUC1: the polymorphic appearance of a human mucin.
2000,
Pubmed
Julian,
Formation of MUC1 metabolic complex is conserved in tumor-derived and normal epithelial cells.
2002,
Pubmed
Khatri,
The carboxyl-terminal sequence of rat intestinal mucin RMuc3 contains a putative transmembrane region and two EGF-like motifs.
1997,
Pubmed
Khatri,
Characteristics of rodent intestinal mucin Muc3 and alterations in a mouse model of human cystic fibrosis.
2001,
Pubmed
Ligtenberg,
Cell-associated episialin is a complex containing two proteins derived from a common precursor.
1992,
Pubmed
McNeer,
Sialomucin complex in the rat respiratory tract: a model for its role in epithelial protection.
1998,
Pubmed
Parmley,
Cystic fibrosis mice lacking Muc1 have reduced amounts of intestinal mucus.
1998,
Pubmed
Parry,
Identification of MUC1 proteolytic cleavage sites in vivo.
2001,
Pubmed
Satyanarayana,
Synthesis and conformational features of human salivary mucin C-terminal derived peptide epitope carrying Thomsen-Friedenreich antigen: implications for its role in self-association.
2001,
Pubmed
Schroeder,
Transgenic MUC1 interacts with epidermal growth factor receptor and correlates with mitogen-activated protein kinase activation in the mouse mammary gland.
2001,
Pubmed
Sheng,
Molecular cloning of the transmembrane component of the 13762 mammary adenocarcinoma sialomucin complex. A new member of the epidermal growth factor superfamily.
1992,
Pubmed
Shirazi,
Mucins and inflammatory bowel disease.
2000,
Pubmed
Smorodinsky,
Detection of a secreted MUC1/SEC protein by MUC1 isoform specific monoclonal antibodies.
1996,
Pubmed
Stacey,
LNB-TM7, a group of seven-transmembrane proteins related to family-B G-protein-coupled receptors.
2000,
Pubmed
Wang,
C-terminal domain of rodent intestinal mucin Muc3 is proteolytically cleaved in the endoplasmic reticulum to generate extracellular and membrane components.
2002,
Pubmed
Wreschner,
Generation of ligand-receptor alliances by "SEA" module-mediated cleavage of membrane-associated mucin proteins.
2002,
Pubmed