PDGFRA 胞外区突变体的信号传导
中文名称
通路描述
受体酪氨酸激酶如 PDGFRA 胞外区的突变可能干扰糖基化，这是正常转运至细胞表面的必要条件。已鉴定出一些癌症中带有胞外区突变的 PDGFRA 版本，虽然其中一些是无活性的，但一些已被证明从内质网持续信号传导（Ip et al, 2018; Velghe et al, 2014; Ozawa et al, 2010; Paugh et al, 2013; Clarke et al, 2003）。PDGFRA Y288C 携带受体胞外区突变，阻止了蛋白正常转运至细胞膜。PDGFRA Y288C 被困在内质网膜中，从该处能够在无配体存在的情况下持续信号传导（Ip et al, 2018）。同样，已鉴定出一种带有外显子 8 和 9 同义缺失的 PDGFRA 版本，在胶质母细胞瘤中发现。产生的蛋白在无配体存在的情况下持续激活，尽管细胞表面蛋白的低比例（Clarke et al, 2003; Ozawa et al, 2010）。
英文描述
Signaling by PDGFRA extracellular domain mutants Mutations in the extracellular domain of receptor tyrosine kinases like PDGRFA have the potential to interfere with glycosylation, which is required for proper trafficking to the cell surface. Versions of PDGFRA bearing mutations in the extracellular domain have been identified in some cancers, and while some of these are inactive, some have also been shown to signal constitutively from the endoplasmic reticulum (Ip et al, 2018; Velghe et al, 2014; Ozawa et al, 2010; Paugh et al, 2013; Clarke et al, 2003). PDGFRA Y288C carries a mutation in the extracellular domain of the receptor that prevents the normal trafficking of the protein to the plasma membrane. PDGFRA Y288C is trapped in the endoplasmic reticulum membrane, from where it is able to signal constitutively in the absence of ligand (Ip et al, 2018). Similarly, a version of PDGFRA bearing an in-frame deletion of exons 8 and 9 has been identified in glioblastoma. The resulting protein is constitutively active in the absence of ligand despite the low fraction of protein expressed at the cell surface (Clarke et al, 2003; Ozawa et al, 2010).
所含基因
7 个基因