Roles of the third Ig-like domain of Necl-5/PVR and the fifth Ig-like domain of the PDGF receptor in its signaling
Roles of the third Ig-like domain of Necl-5/PVR and the fifth Ig-like domain of the PDGF receptor in its signaling
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Necl-5/PVR 的第三个 Ig 样结构域和 PDGF 受体的第五个 Ig 样结构域在其信号传导中的作用
DOI：
10.1111/gtc.12564
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发表时间：
2018
期刊：
影响因子：
2.1
通讯作者：
Takai Yoshimi
中科院分区：
文献类型：
--
作者：
Ueda Yuki;Kedashiro Shin;Maruoka Masahiro;Mizutani Kiyohito;Takai Yoshimi
免疫球蛋白（IG）样细胞粘附分子nectin样分子（Necl）-5/脊髓灰质炎病毒受体在许多类型的癌细胞中上调，并与异常增强的细胞增殖和运动有关。我们先前表明，Necl-5 cis-通过细胞外区域与血小板衍生生长因子（PDGF）受体β相互作用，并增强其信号传导。虽然这种顺式相互作用不影响PDGF诱导的受体酪氨酸磷酸化，但Necl-5的胞质区域与sprouty 2的相互作用及其活性调节是Necl-5增强PDGF受体β信号传导所必需的。我们在这里研究了Necl-5与PDGF受体β的这种顺式相互作用的更详细机制。Necl-5含有三个IG样结构域，PDGF受体β在其细胞外区域含有五个IG样结构域。我们发现Necl-5 cis-的第三个IG样结构域与PDGF受体β的第五个IG样结构域相互作用。Necl-5的第三个IG样结构域的重组蛋白抑制全长Necl-5与PDGF受体β的相互作用以及Necl-5增强的PDGF诱导的ERK信号通路的活化。这些结果揭示了Necl-5的第三个IG样结构域和PDGF受体β的第五个IG样结构域在其信号传导中的新作用。
The immunoglobulin (Ig)‐like cell adhesion molecule nectin‐like molecule (Necl)‐5/poliovirus receptor is up‐regulated in many types of cancer cells and implicated in their abnormally enhanced cell proliferation and movement. We previously showed that Necl‐5cis‐interacts with the platelet‐derived growth factor (PDGF) receptor β through the extracellular region and enhances its signaling. Although thiscis‐interaction does not affect the PDGF‐induced tyrosine phosphorylation of the receptor, the interaction of the cytoplasmic region of Necl‐5 with sprouty2 and the regulation of its activity are required for the enhancement of the PDGF receptor β signaling by Necl‐5. We investigated here the more detailed mechanism for thiscis‐interaction of Necl‐5 with the PDGF receptor β. Necl‐5 contains three Ig‐like domains and the PDGF receptor β contains five Ig‐like domains at their extracellular regions. We showed here that the third Ig‐like domain of Necl‐5cis‐interacted with the fifth Ig‐like domain of the PDGF receptor β. The recombinant protein of the third Ig‐like domain of Necl‐5 inhibited thecis‐interaction of full‐length Necl‐5 with the PDGF receptor β and the PDGF‐induced activation of the ERK signaling pathway that was enhanced by Necl‐5. These results revealed the novel roles of the third Ig‐like domain of Necl‐5 and the fifth Ig‐like domain of the PDGF receptor β in its signaling.