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G蛋白偶联受体(GPCR)可通过多种信号途径激活ERK。其中通过转激活酪氨酸受体是GPCR激活ERK的重要途径之一。我们以前的研究发现阿片受体激动剂DPDPE,TIPP和吗啡能够通过不同的信号途径激活ERK。本研究探讨这些阿片受体激动剂不同的激活ERK是否与它们不同的转激活受体酪氨酸激酶有关及其转激活相关的机制。本研究发现DPDPE,TIPP和吗啡对δ阿片受体转移激活表皮生长因子受体(EGFR)的作用上存在不同的调节效应,发现TIPP和吗啡激动δ阿片受体可引起对EGFR的转移激活,而DPDPE则不能;TIPP和吗啡激动δ阿片受体引起对EGFR的转移激活过程中有PKCδ的参与;GRK磷酸化δ阿片受体的位点丝氨酸363突变可以使原本不引起转移激活的激动剂DPDPE,引起转移激活作用;并且,RNA干扰β-arrestin可以影响EGF刺激EGFR引起的磷酸化ERK信号,故β-arres-tin可能参与转移激活作用。本课题的研究对于深入探索δ阿片受体信号转导的机制有重要的意义。
G-protein coupled receptors (GPCRs) activate ERK through a variety of signaling pathways. Among them, one of the important pathways of activation of ERK by GPCRs is through the activation of tyrosine receptors. Our previous study found that opioid receptor agonists DPDPE, TIPP and morphine can activate ERK through different signaling pathways. This study explored whether these different opioid receptor agonists activate ERK differently depending on their different transactivator receptor tyrosine kinases and their transactivation-related mechanisms. The present study found that DPDPE, TIPP and morphine have different regulatory effects on the activation of epidermal growth factor receptor (EGFR) by δ opioid receptor activation and found that TIPP and morphine agonist δ opioid receptors can cause EGFR metastasis activation, DPDPE can not; TIPP and morphine agonist δ opioid receptor cause EGFR metastasis activation process of PKC δ; GRK phosphorylation of δ opioid receptor serine 363 mutation can make the original did not cause activation of the agonist DPDPE, Β-arrestin can affect EGF-stimulated EGFR-induced phosphorylation of ERK signal, so β-arres-tin may participate in the role of metastasis activation. The research of this topic is of great significance for further exploring the mechanism of δ opioid receptor signal transduction.