Abstract:
: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.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Grøvdal LM,Johannessen LE,Rødland MS,Madshus IH,Stang Edoi
10.1016/j.yexcr.2007.12.017subject
Has Abstractpub_date
2008-04-01 00:00:00pages
1292-300issue
6eissn
0014-4827issn
1090-2422pii
S0014-4827(08)00004-9journal_volume
314pub_type
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