Heregulin degradation in the absence of rapid receptor-mediated internalization

被引:38
作者
Baulida, J
Carpenter, G
机构
[1] VANDERBILT UNIV, SCH MED, DEPT BIOCHEM, NASHVILLE, TN 37232 USA
[2] VANDERBILT UNIV, SCH MED, DEPT MED, NASHVILLE, TN 37232 USA
关键词
EPIDERMAL GROWTH-FACTOR; KINASE-C PHOSPHORYLATION; EGF RECEPTOR; HUMAN-FIBROBLASTS; 3T3; CELLS; PROTEIN; BINDING; TRANSFORMATION; ENDOCYTOSIS;
D O I
10.1006/excr.1997.3515
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 ct al., 1996, J. Biol. Chem. 271, 5251-5257; Pinkas-Kramanski ct 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-S 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. (C) 1997 Academic Press.
引用
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页码:167 / 172
页数:6
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