Oncogenic functions of PTK6 are enhanced by its targeting to plasma membrane but abolished by its targeting to nucleus.
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.
Ie Kim
Han
H
Department of Biochemistry, Yonsei University, Seoul, Republic of Korea.
Lee
Seung-Taek
ST
D017209:Apoptosis; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D049109:Cell Proliferation; D002633:Chemotaxis; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014162:Transfection
D009363:Neoplasm Proteins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; C088375:PTK6 protein, human