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首页> 外文期刊>Cellular Physiology and Biochemistry >Role of ERK, p38 and Pl3-kinase in EGF receptorMediated mitogenic signalling in cultured rat hepatocytes: Requirement for sustained ERK activation
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Role of ERK, p38 and Pl3-kinase in EGF receptorMediated mitogenic signalling in cultured rat hepatocytes: Requirement for sustained ERK activation

机译：ERK，p38和Pl3激酶在EGF受体中的作用在培养的大鼠肝细胞中介导的有丝分裂信号转导：持续ERK激活的要求

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Previous data disagree as to the role of extracellular signal-regulated kinase (ERK) in the EGF receptor-mediated stimulation of proliferation in hepatocytes. Using cultured rat hepatocytes, we here show that EGF receptor stimulation in mid/late G(1) phase caused a sustained ERK activation that lasted for at least 48 h. Inhibition of the early part of this activity by a single addition of the MEK inhibitor PD98059 did not affect the DNA synthesis. However, inhibition of both the early and the sustained phase of ERK activation by washout and repeated administrations of PD98059 abolished the DNA synthesis induced by EGF and TGFalpha. EGF receptor stimulation also transiently activated p38, and inhibition of p38 by SB203580 markedly decreased the DNA synthesis. Furthermore, EGF and TGFalpha stimulated phosphorylation of Akt, a downstream target of the PI3-kinase pathway, and the PI3-kinase inhibitors wortmannin and LY294002 blocked the EGF-induced DNA synthesis. These results support a mechanism for EGF receptor-mediated mitogenic signalling in hepatocytes where ERK has an obligatory role, acting in concert with PI3-kinase, and augmented by p38. Furthermore, the data suggest that to perform this role ERK has to be activated for a prolonged period. Copyright (C) 2003 S. Karger AG, Basel. [References: 51]
机译：先前的数据对于细胞外信号调节激酶（ERK）在EGF受体介导的肝细胞增殖刺激中的作用存在分歧。使用培养的大鼠肝细胞，我们在这里显示中/晚期G（1）期的EGF受体刺激引起持续的ERK激活，持续至少48 h。一次添加MEK抑制剂PD98059抑制该活性的早期部分不影响DNA合成。然而，通过冲洗和重复施用PD98059抑制ERK激活的早期和持续阶段，都消除了EGF和TGFalpha诱导的DNA合成。 EGF受体刺激还可以瞬时激活p38，而SB203580对p38的抑制作用明显降低了DNA的合成。此外，EGF和TGFalpha刺激了PI3激酶途径下游靶点Akt的磷酸化，PI3激酶抑制剂渥曼青霉素和LY294002阻断了EGF诱导的DNA合成。这些结果支持了肝细胞中EGF受体介导的有丝分裂信号转导的机制，其中ERK具有强制性作用，与PI3激酶协同作用，并被p38增强。此外，数据表明，要执行此角色，必须长时间激活ERK。版权所有（C）2003 S.Karger AG，巴塞尔。 [参考：51]

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