PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation

Shin Ae Kang; Seung Taek Lee

doi:10.1016/j.bbrc.2013.01.046

PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation

Shin Ae Kang, Seung Taek Lee

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	734-739
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	431
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2013.01.046
Publication status	Published - 2013

Bibliographical note

Funding 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

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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title = "PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation",

abstract = "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.",

author = "Kang, {Shin Ae} and Lee, {Seung Taek}",

note = "Funding 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. ",

year = "2013",

doi = "10.1016/j.bbrc.2013.01.046",

language = "English",

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journal = "Biochemical and Biophysical Research Communications",

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T1 - PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation

AU - Kang, Shin Ae

AU - Lee, Seung Taek

N1 - Funding 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.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

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DO - 10.1016/j.bbrc.2013.01.046

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VL - 431

SP - 734

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JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation

Abstract

Bibliographical note

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