Modulation of cathepsin D routing by IGF-II involves IGF-II binding to IGF-II/M6P receptor in MCF-7 breast cancer cells.
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.
Faridi
Jesika S
JS
Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Mohan
Subburaman
S
De León
Daisy D
DD
D000818:Animals; D001120:Arginine / Q000737:chemistry; D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism; D002402:Cathepsin D / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D013997:Time Factors; D014162:Transfection
D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D001120:Arginine; D002402:Cathepsin D