Abstract
The IGF-II/M6P receptor targets cathepsin D to the lysosomes and it also binds IGF-II. Although the binding sites for IGF-II and cathepsin D are distinct, reciprocal interactions between the ligands have been observed. We have demonstrated that proIGF-II expression modulates routing of cathepsin D. To test the hypothesis that IGF-II modulation of cathepsin D routing in MCF-7 cells involves IGF-II binding to the IGF-II/M6P receptor, we expressed a mutant form of IGF-II (Arg54 Arg55) that does not bind the IGF-II/M6P receptor and evaluated its effects on cathepsin D secretion. Northern blotting, Western and radioimmunoassay analyses confirmed that these cells express high levels of (Arg54 Arg55) IGF-II mRNA and secretes high levels of IGF-II without modulating the secretion of cathepsin D. These data provide direct evidence that the IGF-II modulation of cathepsin D routing is IGF-II/M6P receptor mediated. © 2004 Taylor & Francis Ltd.
| Original language | English |
|---|---|
| Pages (from-to) | 169-177 |
| Number of pages | 9 |
| Journal | Growth Factors |
| Volume | 22 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 2004 |
ASJC Scopus Subject Areas
- Endocrinology
- Clinical Biochemistry
- Cell Biology
Keywords
- Breast cancer
- Cathepsin D
- Insulin-like growth factor II
- Insulin-like growth factor II/mannose 6-phosphate receptor
- MCF-7
- Arginine/chemistry
- Immunoprecipitation
- Humans
- Immunoblotting
- Insulin-Like Growth Factor II/metabolism
- Dose-Response Relationship, Drug
- Transfection
- Time Factors
- Microsomes, Liver/metabolism
- Radioimmunoassay
- Cell Line
- Cathepsin D/chemistry
- Lysosomes/metabolism
- DNA, Complementary/metabolism
- Blotting, Western
- RNA, Messenger/metabolism
- Blotting, Northern
- Animals
- Culture Media, Conditioned/pharmacology
- Cell Line, Tumor
- Mice
- Genetic Vectors
- Breast Neoplasms/metabolism
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