Journal
EXPERIMENTAL CELL RESEARCH
Volume 314, Issue 6, Pages 1292-1300Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2007.12.017
Keywords
Ack1; EGF receptor; endocytosis; multivesicular body
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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 I-125-EGF internalization, whereas internalization of I-125-transferrin was not affected. In cells where Ack1 had been knocked down by siRNA, recycling of internalized I-125-EGF was increased, while degradation of I-125-EGF was inhibited. Together, these data suggest that Ack1 is involved in an early step of EGFR desensitization. (C) 2008 Elsevier Inc. All rights reserved.
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