Palmitoylation at Cys574 is essential for MT1-MMP to promote cell migration
Palmitoylation at Cys574 is essential for MT1-MMP to promote cell migration
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DOI：
10.1096/fj.04-3651fje
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发表时间：
2005-06-01
期刊：
影响因子：
4.8
通讯作者：
Itoh, Y
中科院分区：
文献类型：
--
作者：
Anilkumar, N;Uekita, T;Itoh, Y
MT 1-MMP是促进细胞迁移和侵袭的I型跨膜蛋白酶。在这里，我们报告，MT 1-MMP是棕榈酰化的Cys（574）在胞质结构域，这种脂质修饰是至关重要的，其促进细胞迁移和网格蛋白介导的内化。棕榈酰化缺陷突变体（C574 A）不能促进细胞迁移，不像野生型那样通过网格蛋白途径内化，但它通过小窝途径内化。在C574 A突变体的胞质尾区的不同位置重新引入半胱氨酸揭示了棕榈酰化半胱氨酸相对于LLY 573的位置，LLY 573是与衔接蛋白2的mu 2亚基相互作用的基序，对于MT 1-MMP的细胞运动促进活性及其网格蛋白介导的内化是至关重要的。总之，MT 1-MMP的棕榈酰化是决定MT 1-MMP依赖性细胞迁移的关键翻译后修饰之一。
MT1-MMP is a type I transmembrane proteinase that promotes cell migration and invasion. Here, we report that MT1-MMP is palmitoylated at Cys(574) in the cytoplasmic domain, and this lipid modification is critical for its promotion of cell migration and clathrin-mediated internalization. The palmitoylation-defective mutant (C574A) failed to promote cell migration and was not internalized through clathrin pathway like wild-type, but it was internalized through the caveolae pathway. Reintroducing a cysteine at different positions in the cytoplasmic tail of the C574A mutant revealed that the position of the palmitoylated cysteine relative to LLY573, a motif that interacts with mu 2 subunit of adaptor protein 2, is critical for the cell motility-promoting activity of MT1-MMP and its clathrin-mediated internalization. Taken together, palmitoylation of MT1-MMP is one of the key posttranslational modifications that determines MT1-MMP-dependent cell migration.