ARAP1 regulates endocytosis of EGFR.
ARAP1 regulates endocytosis of EGFR.
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DOI：
10.1111/j.1600-0854.2008.00839.x
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Randazzo PA
中科院分区：
文献类型：
--
作者：
Yoon HY;Lee JS;Randazzo PA
通过EGF受体的信号传导受内吞作用调节。ARAP 1是具有Arf鸟苷三磷酸酶激活蛋白（GAP）和Rho GAP结构域的蛋白质。我们研究了ARAP 1在EGF受体内吞运输中的作用。EGF处理细胞后，ARAP 1迅速和短暂地与细胞边缘和含有Rab 5、Rabaptin 5和EGFR的点状结构结合，但不与早期胚胎抗原1（EEA 1）结合。EGF与EEA 1阳性早期内体之前的ARAP 1阳性点状结构相关。ARAP 1募集到点状结构需要活性Rab 5和来自EGFR的额外信号。用小干扰RNA降低ARAP 1水平加速EGF与EEA 1内体的结合和EGFR的降解。细胞外信号调节激酶（ERK）和c-Jun氨基末端激酶（JNK）的磷酸化减少，并且在ARAP 1水平降低的细胞中比对照组更短暂。基于这些发现，我们提出ARAP 1调节EGFR的内吞运输，从而调节EGFR信号衰减的速率。
Signaling through the EGF receptor is regulated by endocytosis. ARAP1 is a protein with Arf guanosine triphosphatase-activating protein (GAP) and Rho GAP domains. We investigated the role of ARAP1 in EGF receptor endocytic trafficking. Following EGF treatment of cells, ARAP1 rapidly and transiently associated with the edge of the cell and punctate structures containing Rab5, rabaptin 5 and EGFR but not early embryonic antigen 1 (EEA1). EGF associated with the ARAP1-positive punctate structures prior to EEA1-positive early endosomes. Recruitment of ARAP1 to the punctate structures required active Rab5 and an additional signal from EGFR. Decreasing ARAP1 levels with small interfering RNA accelerated association of EGF with EEA1 endosomes and degradation of EGFR. Phosphorylation of extracellular-signal-regulated kinase (ERK) and c-Jun-amino-terminal kinase (JNK) was diminished and more transient in cells with reduced levels of ARAP1 than in controls. Based on these findings, we propose that ARAP1 regulates the endocytic traffic of EGFR and, consequently, the rate of EGFR signal attenuation.
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DOI：
10.1083/jcb.200806041
发表时间：
2008-09-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kahn RA;Bruford E;Inoue H;Logsdon JM Jr;Nie Z;Premont RT;Randazzo PA;Satake M;Theibert AB;Zapp ML;Cassel D
通讯作者：
Cassel D
影响因子：
3.3
作者：
Cohen, Lee Ann;Honda, Akira;Donaldson, Julie G.
通讯作者：
Donaldson, Julie G.
影响因子：
3.3
作者：
Huang, FT;Sorkin, A
通讯作者：
Sorkin, A
影响因子：
2.1
作者：
Kaneko, T;Maeda, A;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
4.8
作者：
Kremer, W;Steiner, G;Kalbitzer, HR
通讯作者：
Kalbitzer, HR