NOK/STYK1 has a strong tendency towards forming aggregates and colocalises with epidermal growth factor receptor in endosomes
NOK/STYK1 has a strong tendency towards forming aggregates and colocalises with epidermal growth factor receptor in endosomes
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NOK/STYK1 具有形成聚集体的强烈倾向，并与内体中的表皮生长因子受体共定位
DOI：
10.1016/j.bbrc.2012.04.016
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发表时间：
2012-05-11
影响因子：
3.1
通讯作者：
Zhang, Shuping
中科院分区：
文献类型：
--
作者：
Ding, Xue;Jiang, Qing-Bo;Zhang, Shuping
我们前期的研究表明，NOK/STYK 1基因的过表达可导致细胞转化、肿瘤发生和转移。本报告描述了NOK在HeLa细胞中的亚细胞分布及其在早期核内体中的定位。共聚焦免疫定位研究表明，NOK的结构亚型和分布成两个不同的表达模式：一个点模式（DP）和聚集模式（AP）。病理组织的免疫组织化学（IHC）分析的结果也显示内源性NOK的高表达水平在体内以聚集样结构表达。重要的是，我们发现NOK定位于内体，并与表皮生长因子受体（EGFR）共定位于活化的内体囊泡中。然而，随着刺激时间的增加，NOK和EGFR开始通过不同的途径进行。表皮生长因子治疗后，表皮生长因子受体逐渐降解约20分钟，而NOK水平没有降低。这一结果表明，NOK主要在促进EGFR从早期内体向晚期内体/溶酶体的运输中起作用。总之，NOK具有形成聚集体的强烈趋势，这可能具有生理学意义，并提供了这种新型受体激酶与EGFR共定位在内体中以参与EGFR的内化后步骤的第一个证据。(C)2012 Elsevier Inc. All rights reserved.
Our previous studies showed that the overexpression of Novel Oncogene with Kinase-domain (NOK)/STYK1 led to cellular transformation, tumorigenesis and metastasis. This report characterises the subcellular distribution of NOK in HeLa cells and its localisation in early endosomes. Confocal immunolocalisation studies indicated that NOK had structural subtypes and was distributed into two distinct expression patterns: a dot pattern (DP) and an aggregation pattern (AP). The results of an immunohistochemistry (IHC) analysis of pathological tissues also showed that high expression level of endogenous NOK was expressed in an aggregate-like structure in vivo. Importantly, we found that NOK was localised in endosomes and colocalised with epidermal growth factor receptor (EGFR) in activated endosomal vesicles. However, as the stimulation time increased, NOK and EGFR began to progress through different pathways. EGFR was gradually degraded after treatment with EGF for approximately 20 min, whereas NOK levels were not reduced. This result suggests that NOK mainly plays a role in facilitating the trafficking of EGFR from early endosomes to later endosomes/lysosomes. Taken together, NOK has a strong tendency towards forming aggregates, which may have physiological implications and provide the first evidence that this novel receptor kinase is colocalised with EGFR in endosomes to participate in a post-internalisation step of EGFR. (C) 2012 Elsevier Inc. All rights reserved.