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  • Title: Heregulin degradation in the absence of rapid receptor-mediated internalization.
    Author: Baulida J, Carpenter G.
    Journal: Exp Cell Res; 1997 Apr 10; 232(1):167-72. PubMed ID: 9141633.
    Abstract:
    Heregulin receptors are unable to mediate the rapid internalization of bound ligand as demonstrated in cells transfected with chimeric or wild-type ErbB-2, -3, or -4 receptors (Baulida et al., 1996, J. Biol. Chem. 271, 5251-5257; Pinkas-Kramanski et al., 1996, EMBO J. 15, 2452-2467). This observation is now extended to include mammary carcinoma cell lines (SK-BR-3 and MDA-543) which express endogenous ErbB-2 and ErbB-3 receptors. Also, the fate of receptor-bound heregulin is examined. While receptor-bound heregulin is not rapidly internalized, the ligand is subject to a slow process of inactivation and degradation, which requires heregulin incubation at 37 degrees C with cells that express heregulin receptors. The degradation of heregulin is blocked to a significant extent by chloroquine, an inhibitor of endosome fusion with lysosomes, indicating that heregulin is slowly internalized and degraded. However, this process is not sufficiently rapid to produce ligand-dependent down-regulation of heregulin receptors.
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