Muc4/sialomucin complex (SMC) is a heterodimeric glycoprotein complex derived from a single gene that is post-translationally processed into mucin (ASGP-1) and transmembrane (ASGP-2) subunits. Muc4/SMC is tightly regulated in the rat mammary gland, low in the virgin, increased during pregnancy and lactation, and overexpressed in some aggressive mammary tumors. Investigations of primary rat mammary epithelial cells (MEC) have shown that Muc4/SMC expression is post-translationally regulated through inhibition of Muc4/SMC precursor processing by transforming growth factor-beta (TGF-beta). Localization studies suggest that TGF-beta inhibition of Muc4/SMC expression is mediated through SMAD2, a TGF-beta effector that, when activated, functions as a transcription factor. SMAD2 antisense oligonucleotide blocks the inhibition of Muc4/SMC expression by TGF-beta. The TGF-beta effect on Muc4/SMC expression is repressed by interferon-gamma (IFN-gamma). IFN-gamma treatment of MEC activates and relocalizes signal transducer and activator of transcription-1 (STAT-1) to induce an inhibitor SMAD, SMAD7. SMAD7 antisense oligonucleotide prevents IFN-gamma from blocking the TGF-beta inhibition of Muc4/SMC expression. These results suggest that TGF-beta regulates Muc4/SMC expression via the SMAD pathway by a transcriptional effect on a protein in the Muc4/SMC processing step, possibly the protease that cleaves the precursor.
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Expression, location, and interactions of ErbB2 and its intramembrane ligand Muc4 (sialomucin complex) in rat mammary gland during pregnancy.
J Cell Physiol
April 2005
Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida 33101, USA.
Muc4 (also called Sialomucin complex) is a heterodimeric glycoprotein complex consisting of a peripheral O-glycosylated subunit ASGP-1 (ascites sialoglycoprotein-1) tightly but non-covalently bound to an N-glycosylated transmembrane subunit ASGP-2. Muc4/SMC can act as an intramembrane ligand for ErbB2 via an EGF-like domain present in the transmembrane subunit. The complex is developmentally regulated in normal rat mammary gland and overexpressed in a number of mammary tumors.
View Article and Find Full Text PDFNon-apoptotic desquamation of cells from corneal epithelium: putative role for Muc4/sialomucin complex in cell release and survival.
J Cell Physiol
January 2005
Department of Cell Biology, University of Miami School of Medicine, Miami, Florida 33101, USA.
Muc4/sialomucin complex (SMC), a large heterodimeric mucin composed of an extracellular mucin subunit ASGP-1 and a transmembrane subunit ASGP-2, is present at the rat ocular surface localized mainly to the most superficial layers of the epithelia. To investigate corneal homeostasis and the functions of Muc4/SMC at the ocular surface, we developed a corneal epithelial cell culture system from corneal explants, from which migrating cells formed an epithelial sheet resembling the native epithelium with regard to microanatomy, expression of characteristic markers, cell migration, and Muc4/SMC expression. Cells migrating from the explants expressed smooth muscle actin.
View Article and Find Full Text PDFExpression and localization of Muc4/sialomucin complex (SMC) in the adult and developing rat intestine: implications for Muc4/SMC function.
J Cell Physiol
January 2005
Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida 33101, USA.
Muc4/sialomucin complex (SMC) is a high molecular mass heterodimeric membrane mucin, encoded by a single gene, and originally discovered in a highly metastatic ascites rat mammary adenocarcinoma. Subsequent studies have shown that it is a prominent component of many accessible and vulnerable epithelia, including the gastrointestinal tract. Immunoblot and immunofluorescence analyses demonstrated that Muc4/SMC expression in the rat small intestine increases from proximal to distal regions and is located predominantly in cells at the base of the crypts.
View Article and Find Full Text PDFPEA3 transactivates the Muc4/sialomucin complex promoter in mammary epithelial and tumor cells.
J Biol Chem
September 2003
Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida 33101, USA.
Sialomucin complex (SMC, rat Muc4) is a heterodimeric glycoprotein composed of two subunits, the mucin component ascites sialoglycoprotein ASGP-1 and the transmembrane subunit ASGP-2, which is aberrantly expressed on the surfaces of a variety of tumor cells. Up-regulation of the Muc4/SMC gene in the 13762 sublines of the rat mammary adenocarcinoma correlates with the overexpression of transcription factor PEA3 and the receptor tyrosine kinase ErbB2. Here we report that PEA3 is capable of transactivating the Muc4/SMC promoter in a dose-dependent manner via direct attachment to a PEA3 binding site.
View Article and Find Full Text PDFMuc4/sialomucin complex, the intramembrane ErbB2 ligand, translocates ErbB2 to the apical surface in polarized epithelial cells.
J Biol Chem
August 2003
Departments of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida 33101, USA.
Muc4/Sialomucin complex (SMC) acts as an intramembrane ligand for the receptor tyrosine kinase ErbB2, inducing a limited phosphorylation of the receptor. Because Muc4/SMC is found at the apical surfaces of polarized epithelial cells and ErbB2 is often basolateral, the question arises as to whether these components become associated in polarized cells. To address this question, we examined the localization of these proteins in polarized human colon carcinoma CACO-2 cells.
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