Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand.
Bottom Line: Although natural ligands for ErbB2 have not been found, unlike other ErbB receptors, EC-1, a 20-amino acid circular peptide, has been shown to bind to ErbB2 as an artificial ligand.Previously we showed EC-1 peptide did not induce the internalization of ErbB2 in SK-BR-3 cells.Therefore, it is suggested that the multivalent form of EC-1 induces the internalization of ErbB2 through the GEEC pathway.
Affiliation: Laboratory of Nano-Biotechnology, Department of Medical Bioengineering Science, Graduate School of Natural Science and Biotechnology, Okayama University, Kita-ku, Okayama, Japan.Show MeSH
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Mentions: Cells adopt divergent pathways for the endocytosis of the cargos and receptors. The key pathways were categorized into clathrin-dependent and clathrin-independent mechanisms . The clathrin-independent pathway is further classified into caveolar and GPI-anchored early endocytic compartments (GEEC) pathways [33, 34]. ErbB2 is thought to be internalizing in SK-OV-3 through clathrin-mediated internalization . In this study we found that the mechanism of internalization of ErbB2 present in SK-OV-3 cells is deficient in SK-BR-3 cells. We tried to identify the difference between the two cell lines using DNA microarray (Fig. S2). As a result the expression of claudin 16, caveolin-1 and caveolin-2 were found to be extensively down-regulated in SK-BR-3 cells when compared to SK-OV-3 cells. This absence of caveolin-1 in SK-BR-3 cells was further confirmed by immunostaining using anti-Cav1 antibody (Fig. 5A). SK-BR-3 did not show the presence of caveolin-1 suggesting that the impaired caveolar mechanism prevailing in the cell, which was consistent with the finding by the previous reports [13, 35]. Because caveolin-1 was detected in SK-OV-3 cells the internalization pathway deficient in SK-BR-3 cells might be attributed to caveolae.
Affiliation: Laboratory of Nano-Biotechnology, Department of Medical Bioengineering Science, Graduate School of Natural Science and Biotechnology, Okayama University, Kita-ku, Okayama, Japan.