کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2132104 | 1086673 | 2008 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Dysregulation of Ack1 inhibits down-regulation of the EGF receptor Dysregulation of Ack1 inhibits down-regulation of the EGF receptor](/preview/png/2132104.png)
The protein tyrosine kinase Ack1 has been linked to cancer when over-expressed. Ack1 has also been suggested to function in clathrin-mediated endocytosis and in down-regulation of the epidermal growth factor (EGF) receptor (EGFR). We have studied the intracellular localization of over-expressed Ack1 and found that Ack1 co-localizes with the EGFR upon EGF-induced endocytosis in cells with moderate over-expression of Ack. This co-localization is mainly observed in early endosomes. Furthermore, we found that over-expression of Ack1 retained the EGFR at the limiting membrane of early endosomes, inhibiting sorting to inner vesicles of multivesicular bodies. Down-regulation of Ack1 in HeLa cells resulted in reduced rate of 125I-EGF internalization, whereas internalization of 125I-transferrin was not affected. In cells where Ack1 had been knocked down by siRNA, recycling of internalized 125I-EGF was increased, while degradation of 125I-EGF was inhibited. Together, these data suggest that Ack1 is involved in an early step of EGFR desensitization.
Journal: Experimental Cell Research - Volume 314, Issue 6, 1 April 2008, Pages 1292–1300