Muc4/sialomucin complex, the intramembrane ErbB2 ligand, translocates ErbB2 to the apical surface in polarized epithelial cells

Victoria P. Ramsauer, Coralie A.Carothers Carraway, Pedro J.I. Salas, Kermit L. Carraway

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

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. Dual color immunofluorescence analysis by confocal microscopy demonstrated the basolateral localization of the ErbB2 in these cells; it is primarily co-localized with E-cadherin at adherens junctions. Expression of apical Muc4/SMC in these cells by transient transfection results in the localization of the ErbB2 at the apical surface. Two-color confocal microscopy indicated that ErbB2 is colocalized with Muc4/SMC in the transfected cells but not in untransfected cells in the same culture. The change of localization of ErbB2 was confirmed by cell surface biotinylation of apical and basolateral proteins, followed by streptavidin precipitation and the subsequent detection of ErbB2 by immunoblotting. In contrast, Na+/K+-ATPase maintains its basolateral localization in Muc4/SMC-transfected cells, indicating that the translocation of ErbB2 is not the result of depolarization of the cells. A potential physiological role for the apical localization of ErbB2 is indicated by the fact that ErbB2 phosphorylated at tyrosine 1248 is found predominantly in Muc4/SMC-transfected cells, but not in untransfected cells, and is co-localized with the apical Muc4/SMC. The ability of Muc4/SMC to alter the localization of ErbB2, particularly a phosphorylated form of it, in epithelial cells, suggests that it has an important role in regulating ErbB2 signaling.

Original languageEnglish (US)
Pages (from-to)30142-30147
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number32
DOIs
StatePublished - Aug 8 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Muc4/sialomucin complex, the intramembrane ErbB2 ligand, translocates ErbB2 to the apical surface in polarized epithelial cells'. Together they form a unique fingerprint.

  • Cite this