Insulin-like growth factor-binding protein (IGFBP)-3 and IGFBP-5 share a common nuclear transport pathway in T47D human breast carcinoma cells
Insulin-like growth factor-binding protein (IGFBP)-3 and IGFBP-5 share a common nuclear transport pathway in T47D human breast carcinoma cells
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DOI：
10.1074/jbc.273.29.18347
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发表时间：
1998-07-17
影响因子：
4.8
通讯作者：
Baxter, RC
中科院分区：
文献类型：
--
作者：
Schedlich, LJ;Young, TF;Baxter, RC
胰岛素样生长因子结合蛋白（IGFBPs）在多种细胞类型中修饰胰岛素样生长因子的作用中起着不可或缺的作用。最近的证据表明，IGFBP-3和IGFBP-5也对细胞生长具有胰岛素样生长因子非依赖性的影响。在研究这种效应的可能机制时，在T47 D细胞中研究了IGFBP-3和IGFBP-5的细胞内运输，这两种蛋白都含有具有核定位潜力的序列。在一定比例的T47 D细胞中观察到荧光标记的IGFBP-3和IGFBP-5的核摄取，这些细胞似乎正在快速分裂。IGFBP-1和IGFBP-2不具有核转位的推定结构域，不被转运到T47 D细胞的细胞核。当T47 D细胞与过量未标记的IGFBP-3预孵育时，未检测到标记的IGFBP-3或IGFBP-5的核定位，表明它们的核转位涉及共同的途径。抑制受体介导的内吞作用不影响IGFBP-3的核摄取，表明其使用替代的非经典输入途径进行跨质膜转运。此外，IGFBP-3的一个变体形式的突变，在推定的核定位序列不能易位到T47 D细胞的细胞核，这表明IGFBP-3的核易位是依赖于这些羧基末端的碱性残基。
Insulin-like growth factor-binding proteins (IGFBPs) play an integral role in modifying insulin-like growth factor actions in a wide variety of cell types. Recent evidence suggests that IGFBP-3 and IGFBP-5 also have effects on cell growth that are insulin-like growth factor-independent. In investigating possible mechanisms for this effect, the intracellular trafficking of IGFBP-3 and IGFBP-5, both of which contain sequences with the potential for nuclear localization, was studied in T47D cells. Nuclear uptake of fluorescently labeled IGFBP-3 and IGFBP-5 was observed in a proportion of T47D cells that appeared to be rapidly dividing. IGFBP-1 and IGFBP-2, which do not possess the putative domain for nuclear translocation, were not transported to the nuclei of T47D cells. When T47D cells were preincubated with excess unlabeled IGFBP-3, nuclear localization of labeled IGFBP-3 or IGFBP-5 was not detected, indicating that their nuclear translocation involves a common pathway, Inhibition of receptor-mediated endocytosis did not affect nuclear uptake of IGFBP-3, suggesting that it uses an alternative non-classical import pathway for transport across the plasma membrane. In addition, a variant form of IGFBP-3 with a mutation in the putative nuclear localization sequence was unable to translocate to the nuclei of T47D cells, suggesting that nuclear translocation of IGFBP-3 was dependent on these carboxyl-terminal basic residues.