Activation of p38 mitogen-activated protein kinase promotes epidermal growth factor receptor internalization.
Activation of p38 mitogen-activated protein kinase promotes epidermal growth factor receptor internalization.
复制标题
DOI：
10.1111/j.1600-0854.2006.00420.x
复制
发表时间：
2006-06
期刊：
影响因子：
--
通讯作者：
Puertollano R
中科院分区：
文献类型：
--
作者：
Vergarajauregui S;San Miguel A;Puertollano R
细胞内转运在表皮生长因子受体(EGFR)的调节中起着重要作用。为了研究细胞激酶是否调节EGFR的内化，我们使用了山奈霉素，它是哺乳动物细胞中一种强有力的激活剂，尤其是压力激活的丝裂原激活蛋白(MAP)激酶亚型。在这里，我们报告说，苯异霉素p38MAPK的激活足以诱导EGFR内化。茴香素和EGF使用不同的机制来促进EGFR的内吞作用，因为它诱导的内吞不需要酪氨酸激酶活性或受体的泛素化。此外，茴香霉素处理不会导致EGFR在溶酶体的传递和降解。用p38的特异性抑制剂孵育，或用小干扰RNA耗尽内源性的p38，均可阻断山诺霉素诱导的EGFR内化，而对转铁蛋白内吞作用无影响，表明p38激活对EGFR内吞的影响具有特异性。有趣的是，抑制p38的激活也取消了紫外线诱导的EGFR的内吞作用。我们的结果揭示了p38在调节EGFR内吞作用中的新作用，并提示p38刺激EGFR内化可能是在应激条件下阻止增殖或抗凋亡信号产生的一般机制。
Endocytic trafficking plays an important role in the regulation of the epidermal growth factor receptor (EGFR). To address if cellular kinases regulate EGFR internalization, we used anisomycin, a potent activator of kinase cascades in mammalian cells, especially the stress-activated mitogen-activated protein (MAP) kinase subtypes. Here, we report that activation of p38 MAP kinase by anisomycin is sufficient to induce internalization of EGFR. Anisomycin and EGF employ different mechanisms to promote EGFR endocytosis as anisomycin-induced internalization does not require tyrosine kinase activity or ubiquitination of the receptor. In addition, anisomycin treatment did not result in delivery and degradation of EGFR at lysosomes. Incubation with a specific inhibitor of p38, or depletion of endogenous p38 by small interfering RNAs, abolished anisomycin-induced internalization of EGFR while having no effect on transferrin endocytosis, indicating that the effect of p38 activation on EGFR endocytosis is specific. Interestingly, inhibition of p38 activation also abolished endocytosis of EGFR induced by UV radiation. Our results reveal a novel role for p38 in the regulation of EGFR endocytosis and suggest that stimulation of EGFR internalization by p38 might represent a general mechanism to prevent generation of proliferative or anti-apoptotic signals under stress conditions.
登录
查看更多内容
影响因子：
56.9
作者：
HAN, J;LEE, JD;ULEVITCH, RJ
通讯作者：
ULEVITCH, RJ
影响因子：
10.5
作者：
Brancho, D;Tanaka, N;Davis, RJ
通讯作者：
Davis, RJ
影响因子：
11.4
作者：
Beyaert, R;Cuenda, A;Fiers, W
通讯作者：
Fiers, W
影响因子：
21.3
作者：
Haglund, K;Sigismund, S;Dikic, I
通讯作者：
Dikic, I
影响因子：
4.8
作者：
Carter, RE;Sorkin, A
通讯作者：
Sorkin, A