PTK6 (also known as Brk) is an intracellular tyrosine kinase which induces proliferation, anti-apoptosis, migration, and anchorage-independent growth. Herein we report that PTK6 phosphorylates and down-regulates E3 ubiquitin ligase c-Cbl. Tyr700, Tyr731, and Tyr774 residues in the C-terminal domain of c-Cbl are major phosphorylation sites targeted by PTK6. The phosphorylated c-Cbl is subjected to auto-ubiquitination and degraded through the ubiquitin-proteasome pathway. These results provide evidence for a novel mechanism demonstrating the oncogenic potential of PTK6 through degradation of c-Cbl, which is an E3 ligase important in down-regulation of oncoproteins.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2013|
Bibliographical noteFunding Information:
This work was supported by a Grant from the National Research Foundation, Ministry of Education, Science, and Technology, Republic of Korea through the project for Studies on Ubiquitome Functions ( M10533010001-05N3301 ) and the Basic Research Program ( 2012R1A1A2007638 ), and by a Seoul Research and Business Development Grant ( 10527 ). S.-A.K. was a pre-doctoral trainee and a post-doctoral trainee of the Brain Korea 21 program from the Ministry of Education, Science, and Technology, Republic of Korea.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology