Internalization of EGF Receptor Following Lipid Rafts Disruption in Keratinocytes Is Delayed and Dependent on p38 MAPK Activation
Internalization of EGF Receptor Following Lipid Rafts Disruption in Keratinocytes Is Delayed and Dependent on p38 MAPK Activation
复制标题
DOI：
10.1002/jcp.21563
复制
发表时间：
2008-12-01
影响因子：
5.6
通讯作者：
Poumay, Yves
中科院分区：
文献类型：
--
作者：
Lambert, Sylviane;Ameels, Helene;Poumay, Yves
表皮生长因子（EGF）受体在表皮角质形成细胞中起重要作用，已知在胆固醇消耗后，表皮生长因子受体会从脂质筏中移出，导致配体非依赖性激活。越来越多的证据表明，在应激条件下，在p38 MAPK的控制下，EGF受体（EGFR）在没有配体参与的情况下进行内化的能力。由于已知甲基- β -环糊精消耗胆固醇可诱导角化细胞中不依赖配体的EGFR激活，我们通过共聚焦显微镜和配体结合试验研究了脂筏破坏后EGFR的加工和定位。在这里，我们报道了受体的二聚化和缓慢内化，伴随着酪氨酸1068的延迟磷酸化及其被蛋白酶体降解。我们还证明了p38 MAPK参与内化过程，这可以被认为是对应激的保护性反应。此外，在脂质筏破坏后的恢复期，胆固醇耗尽的角质形成细胞恢复其增殖能力。
The receptor for epidermal growth factor (EGF) plays an important role in epidermal keratinocytes and is known to move out of lipid raft after cholesterol depletion, leading to ligand-independent activation. Accumulation of evidence indicates the ability of EGF receptor (EGFR) to undergo internalization without participation of the ligand under the control of p38 MAPK during stress conditions. Since cholesterol depletion using methyl-beta-cyclodextrin is known to induce ligand-independent activation of EGFR in keratinocytes, we investigated by confocal microscopy and ligand-binding tests the processing and localization of EGFR following lipid raft disruption. Here, we report the dimerization and the slow internalization of the receptor accompanied by the delayed phosphorylation of tyrosine 1068 and its degradation by the proteasome. We also demonstrate the involvement of p38 MAPK during the process of internalization, which can be considered as a protective response to stress. Moreover, cholesterol-depleted keratinocytes recover their ability to proliferate during the recovery period that follows lipid raft disruption.