trk受体
原肌球蛋白受体激酶B
融合蛋白
细胞生物学
受体酪氨酸激酶
信号转导
原肌球蛋白
神经营养素
激酶
生物
酪氨酸激酶
融合基因
受体
化学
基因
神经营养因子
生物化学
肌动蛋白
重组DNA
作者
Tianxin Zhu,Jingjing Xie,Hanqing He,Huan Li,Xianbin Tang,Shuyang Wang,Ziwen Li,Yaguang Tian,Ren Xiang Tan,Jidong Zhu,Guangya Zhu
标识
DOI:10.1073/pnas.2219589120
摘要
NTRK (neurotrophic tyrosine receptor kinase) gene fusions that encode chimeric proteins exhibiting constitutive activity of tropomyosin receptor kinases (TRK), are oncogenic drivers in multiple cancer types. However, the underlying mechanisms in oncogenesis that involve various N-terminal fusion partners of NTRK fusions remain elusive. Here, we show that NTRK fusion proteins form liquid-like condensates driven by their N-terminal fusion partners. The kinase reactions are accelerated in these condensates where the complexes for downstream signaling activation are also concentrated. Our work demonstrates that the phase separation driven by NTRK fusions is not only critical for TRK activation, but the condensates formed through phase separation serve as organizational hubs for oncogenic signaling.
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