XK相关蛋白5（XKR5）是KIT/D816V介导的细胞转化的新型负调控因子。
XK-related protein 5 (XKR5) is a novel negative regulator of KIT/D816V-mediated transformation.
作者信息
Sun Jianmin, Thingholm Tine, Højrup Peter, Rönnstrand Lars
机构信息
Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
Department of Laboratory Medicine, Translational Cancer Research, Lund University, Lund, Sweden.
出版信息
Oncogenesis. 2018 Jun 18;7(6):48. doi: 10.1038/s41389-018-0057-3.
In order to investigate the molecular mechanisms by which the oncogenic mutant KIT/D816V causes transformation of cells, we investigated proteins that selectively bind KIT/D816V, but not wild-type KIT, as potential mediators of transformation. By mass spectrometry several proteins were identified, among them a previously uncharacterized protein denoted XKR5 (XK-related protein 5), which is related to the X Kell blood group proteins. We could demonstrate that interaction between XKR5 and KIT/D816V leads to phosphorylation of XKR5 at Tyr 369, Tyr487, and Tyr 543. Tyrosine phosphorylated XKR5 acts as a negative regulator of KIT signaling, which leads to downregulation of phosphorylation of ERK, AKT, and p38. This led to reduced proliferation and colony forming capacity in semi-solid medium. Taken together, our data demonstrate that XKR5 is a novel type of negative regulator of KIT-mediated transformation.
为了研究致癌突变体KIT/D816V导致细胞转化的分子机制，我们研究了选择性结合KIT/D816V而非野生型KIT的蛋白质，将其作为转化的潜在介质。通过质谱鉴定了几种蛋白质，其中包括一种以前未表征的蛋白质，称为XKR5（XK相关蛋白5），它与X Kell血型蛋白相关。我们可以证明XKR5与KIT/D816V之间的相互作用导致XKR5在酪氨酸369、酪氨酸487和酪氨酸543处磷酸化。酪氨酸磷酸化的XKR5作为KIT信号的负调节因子，导致ERK、AKT和p38磷酸化的下调。这导致在半固体培养基中增殖和集落形成能力降低。综上所述，我们的数据表明XKR5是KIT介导的转化的新型负调节因子。
Zotero 插件