Dysregulation of Ack1 inhibits down-regulation of the EGF receptor

Exp Cell Res. 2008 Apr 1;314(6):1292-300. doi: 10.1016/j.yexcr.2007.12.017. Epub 2008 Jan 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Compartmentation
  • Clathrin / metabolism
  • Clathrin / ultrastructure
  • Down-Regulation*
  • Endocytosis
  • Endosomes / metabolism
  • Endosomes / ultrastructure
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / metabolism*
  • HeLa Cells
  • Humans
  • Iodine Radioisotopes
  • Membrane Proteins / metabolism
  • Protein Transport
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / metabolism*
  • Protein-Tyrosine Kinases / ultrastructure
  • RNA, Small Interfering / metabolism
  • Vesicular Transport Proteins / metabolism


  • Clathrin
  • Iodine Radioisotopes
  • Membrane Proteins
  • RNA, Small Interfering
  • Vesicular Transport Proteins
  • early endosome antigen 1
  • Epidermal Growth Factor
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • TNK2 protein, human