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Journal of Biochemistry Advance Access originally published online on March 20, 2009
Journal of Biochemistry 2009 146(1):133-139; doi:10.1093/jb/mvp050
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© The Authors 2009. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved

Oncogenic Functions of PTK6 are Enhanced by Its Targeting to Plasma Membrane But Abolished by Its Targeting to Nucleus

Han Ie Kim and Seung-Taek Lee*

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea

*To whom correspondence should be addressed. Tel: +82-2-2123-2703, Fax: +82-2-362-9897, E-mail: stlee{at}yonsei.ac.kr

Received December 13, 2008; Accepted March 12, 2009


   Abstract

PTK6 (also known as Brk) is an intracellular tyrosine kinase whose expression is up-regulated in several tumour types. Because localization of protein tyrosine kinases plays an important role in the development of cancers, we investigated the relationship between subcellular localization of PTK6 and its oncogenic properties. PTK6 was targeted to the plasma membrane or the nucleus of HEK 293 cells using the Src myristoylation signal (Myr) or SV40 T-antigen nuclear localization signal (NLS), respectively. The profile of cellular proteins phosphorylated by Myr-PTK6 was quite different from those phosphorylated by NLS-PTK6. Localization of PTK6 to the plasma membrane enhanced the ability of PTK6 to promote proliferation, cell survival and migration and to permit anchorage-independent colony formation. In contrast, nuclear localization of PTK6 impaired these functions. Our results demonstrate that recruitment of PTK6 to the plasma membrane is required for oncogenic function.

Key Words: Brk, myristoylation, nuclear localization, oncogene, PTK6, subcellular localization, tyrosine kinase

Abbreviations: DAPI, 4',6-diamidino-2-phenylindole; DMEM, Dulbecco's Modified Eagle Medium; FBS, fetal bovine serum; Myr, myristoylation signal; NLS, nuclear localization signal; OSCC, oral squamous cell carcinoma; TUNEL, terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling


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