Regulation of O-glycosylation through Golgi-to-ER relocation of initiation enzymes.
Regulation of O-glycosylation through Golgi-to-ER relocation of initiation enzymes.
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DOI：
10.1083/jcb.201003055
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发表时间：
2010-05-31
期刊：
影响因子：
--
通讯作者：
Bard F
中科院分区：
文献类型：
--
作者：
Gill DJ;Chia J;Senewiratne J;Bard F
生长因子刺激将o -糖基化起始酶（GalNac-Ts）以src依赖的方式从高尔基体转移到内质网，增加蛋白质o -糖基化。在生长因子刺激后，激酶被激活来调节细胞生理的多个方面。活化的Src存在于高尔基膜上，但其在这里的功能尚不清楚。我们发现Src通过启动酶（多肽n-乙酰半乳糖氨基转移酶（GalNac-Ts））从高尔基体到内质网的再分配来调节粘蛋白型蛋白的o糖基化。再分配发生在EGF或PDGF以Src依赖的方式刺激后，以及Src活性组成性升高的细胞中。所有测试的GalNac-T家族酶都受到影响，而其他多种糖基化酶不会从高尔基体中转移。Src激活后，cop - 1外壳也重新分布在点状结构中，这些点状结构与GalNac-Ts和Arf1显性阴性异构体Arf1（Q71L）共定位，有效地阻断GalNac-T的再分布，表明Src激活了cop - 1依赖性转运事件。最后，凝集素染色和代谢标记显示，Src激活增加了o -糖基化起始。我们提出，生长因子刺激通过GalNac-T再分配到内质网，以src依赖的方式调节o糖基化起始。
Growth factor stimulation moves O-glycosylation initiation enzymes (GalNac-Ts) from the Golgi to the ER in a Src-dependent fashion, increasing protein O-glycosylation. After growth factor stimulation, kinases are activated to regulate multiple aspects of cell physiology. Activated Src is present on Golgi membranes, but its function here remains unclear. We find that Src regulates mucin-type protein O-glycosylation through redistribution of the initiating enzymes, polypeptide N-acetylgalactosaminyl transferases (GalNac-Ts), from the Golgi to the ER. Redistribution occurs after stimulation with EGF or PDGF in a Src-dependent manner and in cells with constitutively elevated Src activity. All GalNac-T family enzymes tested are affected, whereas multiple other glycosylation enzymes are not displaced from the Golgi. Upon Src activation, the COP-I coat is also redistributed in punctate structures that colocalize with GalNac-Ts and a dominant-negative Arf1 isoform, Arf1(Q71L), efficiently blocks GalNac-T redistribution, indicating that Src activates a COP-I–dependent trafficking event. Finally, Src activation increases O-glycosylation initiation as seen by lectin staining and metabolic labeling. We propose that growth factor stimulation regulates O-glycosylation initiation in a Src-dependent fashion by GalNac-T redistribution to the ER.
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影响因子：
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