Glycan-deficient PrP stimulates VEGFR2 signaling via glycosaminoglycan.
Glycan-deficient PrP stimulates VEGFR2 signaling via glycosaminoglycan.
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DOI：
10.1016/j.cellsig.2016.03.010
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发表时间：
2016-06
影响因子：
4.8
通讯作者：
Zhenxing Gao;Huixia Zhang;Fei Hu;Liheng Yang;Xiaowen Yang;Ying Zhu;M. Sy;Chaoyang Li
中科院分区：
文献类型：
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作者：
Zhenxing Gao;Huixia Zhang;Fei Hu;Liheng Yang;Xiaowen Yang;Ying Zhu;M. Sy;Chaoyang Li
这两个N-连接的聚糖在朊病毒、PrP生物学中是否重要还没有解决。在中国仓鼠卵巢（CHO）细胞中，这两种聚糖在转染人PrP的细胞表面表达中显然不重要。与完全糖基化的PrP相比，聚糖缺陷的PrP优先分配到脂筏。在CHO细胞中，聚糖缺陷型PrP还与糖胺聚糖（GAG）和血管内皮生长因子受体2（VEGFR2）相互作用，导致VEGFR2活化和Akt磷酸化增强。因此，表达缺乏GAG结合基序的聚糖缺陷型PrP的CHO细胞或用肝素酶处理以去除GAG的细胞显示Akt信号传导减弱。在脂筏中是至关重要的，具有CD4跨膜和胞质结构域的嵌合聚糖缺陷型PrP在脂筏中不存在，并且不激活Akt信号传导。携带聚糖缺陷型PrP的CHO细胞也表现出增强的细胞粘附和迁移。基于这些发现，我们提出了一个模型，其中聚糖缺陷PrP，GAG和VEGFR2相互作用，激活VEGFR2，导致细胞行为的变化。
Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. Compared to fully-glycosylated PrP, glycan-deficient PrP preferentially partitions to lipid raft. In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. Accordingly, CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG show diminished Akt signaling. Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. CHO cells bearing glycan-deficient PrP also exhibit enhanced cellular adhesion and migration. Based on these findings, we propose a model in which glycan-deficient PrP, GAG, and VEGFR2 interact, activating VEGFR2 and resulting in changes in cellular behavior.