Modulation of cathepsin D routing by IGF-II involves IGF-II binding to IGF-II/M6P receptor in MCF-7 breast cancer cells.
Modulation of cathepsin D routing by IGF-II involves IGF-II binding to IGF-II/M6P receptor in MCF-7 breast cancer cells.
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IGF-II 对组织蛋白酶 D 路径的调节涉及 IGF-II 与 MCF-7 乳腺癌细胞中的 IGF-II/M6P 受体的结合。
DOI：
10.1080/08977190410001725531
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
DeLeon,DaisyD
中科院分区：
文献类型：
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作者：
Faridi,JesikaS;Mohan,Subburaman;DeLeon,DaisyD
IGF-II/M6 P受体将组织蛋白酶D靶向至溶酶体，并且其也结合IGF-II。虽然IGF-II和组织蛋白酶D的结合位点不同，但已观察到配体之间的相互作用。我们已经证明proIGF-II表达调节组织蛋白酶D的途径。为了检验IGF-Ⅱ对MCF-7细胞中组织蛋白酶D的调节涉及IGF-Ⅱ与IGF-Ⅱ/M6 P受体结合的假设，我们表达了一种不与IGF-Ⅱ/M6 P受体结合的IGF-Ⅱ突变体（Arg 54 Arg 55），并评价了其对组织蛋白酶D分泌的影响。北方印迹、Western和放射免疫分析证实，这些细胞表达高水平的（Arg 54 Arg 55）IGF-II mRNA，并分泌高水平的IGF-II，而不调节组织蛋白酶D的分泌。这些数据提供了直接的证据，IGF-II调节组织蛋白酶D的路由是IGF-II/M6 P受体介导的。
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 (Arg54Arg55) 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 (Arg54Arg55) 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.