Dysregulation of Ack1 inhibits down-regulation of the EGF receptor
- University of Oslo, Institute of Pathology, Rikshospitalet HF, 0027 Oslo (Norway)
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 {sup 125}I-EGF internalization, whereas internalization of {sup 125}I-transferrin was not affected. In cells where Ack1 had been knocked down by siRNA, recycling of internalized {sup 125}I-EGF was increased, while degradation of {sup 125}I-EGF was inhibited. Together, these data suggest that Ack1 is involved in an early step of EGFR desensitization.
- OSTI ID:
- 21045960
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 6 Vol. 314; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
Similar Records
Effect of the anti-receptor ligand-blocking 225 monoclonal antibody on EGF receptor endocytosis and sorting
EGF Receptor Sorting in Endosomal Compartments