Dysregulation of Ack1 inhibits down-regulation of the EGF receptor.

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 (125)I-EGF internalization, whereas internalization of (125)I-transferrin was not affected. In cells where Ack1 had been knocked down by siRNA, recycling of internalized (125)I-EGF was increased, while degradation of (125)I-EGF was inhibited. Together, these data suggest that Ack1 is involved in an early step of EGFR desensitization.
Mesh Terms:
Cell Compartmentation, Clathrin, Down-Regulation, Endocytosis, Endosomes, Epidermal Growth Factor, HeLa Cells, Humans, Iodine Radioisotopes, Membrane Proteins, Protein Transport, Protein-Tyrosine Kinases, RNA, Small Interfering, Receptor, Epidermal Growth Factor, Vesicular Transport Proteins
Exp. Cell Res.
Date: Apr. 01, 2008
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