Univ. Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France.
Inserm U1003-PHYCEL-Cellular Physiology, University of Lille, Lille, France.
FEBS Lett. 2021 Nov;595(21):2655-2664. doi: 10.1002/1873-3468.14195. Epub 2021 Oct 10.
The high-affinity tyrosine kinase receptor MET plays a pivotal role in several facets of cell regulation. Although its mitogenic effect is well documented, some aspects of connection patterns between signaling pathways involved in cell cycle progression remain to be deciphered. We have used a tractable heterologous expression system, the Xenopus oocyte, to detect connections between distinct MET signaling cascades involved in G2/M progression. Our results reveal that Src acts as an adapter via its SH2 domain to recruit 3-phosphoinositide-dependent protein kinase 1 (PDK1) to the MET signaling complex leading to Akt phosphorylation. These data define an original crosstalk between Src and Akt signaling pathways that contributes to MET-induced entry into the M phase, and deserves further investigation in pathologies harboring deregulation of this receptor.
高亲和力酪氨酸激酶受体 MET 在细胞调节的几个方面发挥着关键作用。虽然它的促有丝分裂作用已有充分的记录，但细胞周期进程中涉及的信号通路之间的连接模式的某些方面仍有待破译。我们使用了一种易于处理的异源表达系统，即非洲爪蟾卵母细胞，来检测参与 G2/M 进展的不同 MET 信号级联之间的连接。我们的结果表明，Src 通过其 SH2 结构域作为衔接蛋白，将 3-磷酸肌醇依赖性蛋白激酶 1（PDK1）募集到 MET 信号复合物中，导致 Akt 磷酸化。这些数据定义了Src 和 Akt 信号通路之间的原始串扰，有助于 MET 诱导进入 M 期，在存在该受体失调的病理中值得进一步研究。
