A scaffold protein JIP-1b enhances amyloid precursor protein phosphorylation by JNK and its association with kinesin light chain 1
A scaffold protein JIP-1b enhances amyloid precursor protein phosphorylation by JNK and its association with kinesin light chain 1
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DOI：
10.1074/jbc.m212160200
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发表时间：
2003-06-20
影响因子：
4.8
通讯作者：
Kitamura, N
中科院分区：
文献类型：
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作者：
Inomata, H;Nakamura, Y;Kitamura, N
淀粉样前体蛋白(APP)是β-淀粉样多肽的前体分子，是阿尔茨海默病患者淀粉样斑块的主要成分。在本研究中，我们分离了JNK信号骨架蛋白JIP-1b作为APP的结合蛋白，并分析了JIP-1b在JNK对APP磷酸化过程中的作用以及Kinesin轻链1与APP的关系。JNK可促进JIP-1b支架上和外源表达APP的培养细胞中668位苏氨酸的APP磷酸化。神经生长因子诱导的PC12细胞中APP的磷酸化是通过激活JNK信号途径实现的。Jip-1b还增强了Kinesin轻链1与APP的联系。我们的结果表明，JIP-1b可能是一种连接Kinesin-I马达蛋白和货物受体APP的蛋白质，JNK信号通路可能通过JIP-1b支架调节该货物蛋白的磷酸化。
Amyloid precursor protein (APP) is the precursor molecule of beta-amyloid peptides, the major components of amyloid plaque in patients with Alzheimer's disease. In this study, we isolated JIP-1b, a JNK signaling scaffold protein, as a binding protein of APP, and analyzed the roles of JIP-1b in APP phosphorylation by JNK and the association of kinesin light chain 1 with APP. APP phosphorylation at threonine 668 by JNK was enhanced on the JIP-1b scaffold in vitro and in cultured cells exogenously expressing APP. APP phosphorylation in nerve growth factor-differentiated PC12 cells was mediated by activation of JNK signaling. JIP-1b also enhanced the association of kinesin light chain 1 with APP. Our results suggest that JIP-1b may function as a protein linking the kinesin-I motor protein to the cargo receptor, APP, and that the JNK signaling pathway may regulate the phosphorylation of this cargo protein through the JIP-1b scaffold.