Regulation of platelet-derived growth factor-induced Ras signaling by poliovirus receptor Necl-5 and negative growth regulator Sprouty2
Regulation of platelet-derived growth factor-induced Ras signaling by poliovirus receptor Necl-5 and negative growth regulator Sprouty2
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DOI：
10.1111/j.1365-2443.2007.01062.x
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发表时间：
2007-03-01
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：
Kajita, Mihoko;Ikeda, Wataru;Takai, Yoshimi
Necl-5被称为脊髓灰质炎病毒受体，在许多癌细胞中上调，增强血小板衍生生长因子（PDGF）诱导的Ras-Raf-MEK-ERK信号的激活，但不增强PDGF诱导的PDGF受体酪氨酸磷酸化，从而促进细胞增殖。在这里，我们发现Necl-5与Sprouty2相互作用，降低了Sprouty2对pdgf诱导的Ras信号的抑制作用。Sprouty2是生长因子诱导的信号传导的负调节因子。据报道，在细胞-细胞接触时，Necl-5通过与nectin-3的反式相互作用而下调，从而启动与钙粘蛋白的协同细胞-细胞粘附。Necl-5的下调引起c-Src对Sprouty2的酪氨酸磷酸化，PDGF受体响应PDGF激活Sprouty2，抑制PDGF诱导的Ras信号传导。因此，Necl-5和Sprouty2协同调节pdgf诱导的Ras信号。讨论了Necl-5和Sprouty2在接触抑制细胞增殖中的作用。
Necl-5, known as a poliovirus receptor and up-regulated in many cancer cells, enhances platelet-derived growth factor (PDGF)-induced activation of Ras-Raf-MEK-ERK signaling, but not PDGF-induced tyrosine phosphorylation of PDGF receptor, resulting in facilitation of cell proliferation. Here, we showed that Necl-5 interacted with Sprouty2, known to be a negative regulator of growth factor-induced signaling, and reduced the inhibitory effect of Sprouty2 on PDGF-induced Ras signaling. Necl-5 was reported to be down-regulated by its trans-interaction with nectin-3 upon cell-cell contact, initiating cooperative cell-cell adhesion with cadherin. This down-regulation of Necl-5 caused tyrosine phosphorylation of Sprouty2 by c-Src, which was activated by PDGF receptor in response to PDGF, and inhibited PDGF-induced Ras signaling. Thus, Necl-5 and Sprouty2 cooperatively regulate PDGF-induced Ras signaling. The roles of Necl-5 and Sprouty2 in contact inhibition for cell proliferation are also discussed.