Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways.

Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways. Abstract Text:

Scott Jepson,Masanobu Komatsu,Bushra Haq,Maria E Arango,Daming Huang,Coralie A Carothers Carraway,Kermit L Carraway,

Muc4/sialomucin complex (SMC) is a multifunctional glycoprotein complex which can repress apoptosis in transfected tumor cells. Its transmembrane subunit acts as an intramembrane ligand for the receptor tyrosine kinase ErbB2 to induce the phosphorylation of ErbB2 and, by acting synergistically with the ErbB3 ligand neuregulin, can potentiate the phosphorylation of ErbB2 and ErbB3. In the present study we show that Muc4/SMC alone robustly induces the phosphorylation of ErbB2 to enhance the tyrosine phosphate epitope (Tyr1248) recognized by anti-phospho-ErbB2. Although this tyrosine phosphorylation has been implicated in cell transformation, it does not activate any of the three mitogen-activated protein kinases (MAPKs) or protein kinase B/Akt of the phosphatidyl inositol 3-kinase pathway. Instead, Muc4/SMC expression induces up-regulation of the cell cycle inhibitor p27(kip), consistent with the expression of Muc4/SMC in differentiated, rather than proliferative, epithelial cells. Interestingly, a combination of Muc4/SMC and neuregulin down-regulate p27(kip) and activate protein kinase B/Akt. These observations suggest that Muc4/SMC acts as a regulator of differentiation by inducing a limited phosphorylation of ErbB2 and a modulator of proliferation when acting synergistically with neuregulin to induce a more extensive phosphorylation on both ErbB2 and ErbB3.

Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways. Publishing Authors By Initials

S Jepson,M Komatsu,B Haq,ME Arango,D Huang,CA Carraway,KL Carraway,

For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

PUBMED ID PMID:

MEDLINE DATE:

Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Oncogene

VOLUME: 21

Page Numbers: 7524-32

Journal Abbreviation: Oncogene

ISSN: 0950-9232

DAY: 24

MONTH: Oct

YEAR: 2002

Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8711562

Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways. Keywords Mesh Terms:

KEYWORDS: Up-Regulation

MESH TERMS: metabolism

Chemical & Substance for Abstract: Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways. Information

Substance Name: Mitogen-Activated Protein Kinases

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways.

AFFILIATION: Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida, FL 33101, USA.

Country: England

AGENCY: United States NCI

GRANT: CA74072

ACRONYM: CA

MEDLINETA: Oncogene

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27kip, but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways Related Publications

• An ErbB2-Muc4 complex in rat ocular surface epithelia.
• Cloning and characterization of the 5' flanking region of the sialomucin complex/rat Muc4 gene: promoter activity in cultured cells.
• Detection of sialomucin complex (MUC4) in human ocular surface epithelium and tear fluid.
• Differential localization of ErbB2 in different tissues of the rat female reproductive tract: implications for the use of specific antibodies for ErbB2 analysis.
• ErbB2 and its ligand Muc4 (sialomucin complex) in rat lacrimal gland.
• Expression and localization of Muc4/sialomucin complex (SMC) in the adult and developing rat intestine: implications for Muc4/SMC function.
• Expression and localization of immunoreactive-sialomucin complex (Muc4) in salivary glands.
• Extracellular regulated kinase (ERK)-dependent regulation of sialomucin complex/rat Muc4 in mammary epithelial cells.
• MUC4 (sialomucin complex) expression in salivary gland tumors and squamous cell carcinoma of the upper aerodigestive tract.
• MUC4 and ERBB2 expression in major and minor salivary gland mucoepidermoid carcinoma.
• MUC4 and ErbB2 expression in squamous cell carcinoma of the upper aerodigestive tract: correlation with clinical outcomes.
• Muc4/sialomucin complex in the mammary gland and breast cancer.
• Muc4/sialomucin complex, the intramembrane ErbB2 ligand, in cancer and epithelia: to protect and to survive.
• Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways.
• Muc4/sialomucin complex, the intramembrane ErbB2 ligand, translocates ErbB2 to the apical surface in polarized epithelial cells.
• Multiple facets of sialomucin complex/MUC4, a membrane mucin and erbb2 ligand, in tumors and tissues (Y2K update).
• Non-apoptotic desquamation of cells from corneal epithelium: putative role for Muc4/sialomucin complex in cell release and survival.
• Overexpression of sialomucin complex, a rat homologue of MUC4, inhibits tumor killing by lymphokine-activated killer cells.
• PEA3 transactivates the Muc4/sialomucin complex promoter in mammary epithelial and tumor cells.
• Post-transcriptional regulation of a milk membrane protein, the sialomucin complex (Ascites sialoglycoprotein (ASGP)-1/ASGP-2, rat muc4), by transforming growth factor beta.
• Potentiation of metastasis by cell surface sialomucin complex (rat MUC4), a multifunctional anti-adhesive glycoprotein.
• Production and localization of Muc4/sialomucin complex and its receptor tyrosine kinase ErbB2 in the rat lacrimal gland.
• Rat Muc4 (sialomucin complex) reduces binding of anti-ErbB2 antibodies to tumor cell surfaces, a potential mechanism for herceptin resistance.
• Regulation of sialomucin complex/Muc4 expression in rat uterine luminal epithelial cells by transforming growth factor-beta: implications for blastocyst implantation.
• SMAD2 and SMAD7 involvement in the post-translational regulation of Muc4 via the transforming growth factor-beta and interferon-gamma pathways in rat mammary epithelial cells.
• Sialomucin complex (Muc4) expression in the rat female reproductive tract.
• Sialomucin complex (rMuc4) expression during development of the rat cornea.
• Sialomucin complex (rat Muc4) is regulated by transforming growth factor beta in mammary gland by a novel post-translational mechanism.
• Sialomucin complex (rat Muc4) transmembrane subunit binds the differentiation marker peanut lectin in the normal rat mammary gland.
• Synthesis and secretion of Muc4/sialomucin complex: implication of intracellular proteolysis.