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J Cell Biochem. 2017 Sep;118(9):2887-2895. doi: 10.1002/jcb.25939. Epub 2017 May 15.

PTK6 Localized at the Plasma Membrane Promotes Cell Proliferation and MigratiOn Through Phosphorylation of Eps8.

Author information

1
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.

Abstract

Protein tyrosine kinase 6 (PTK6; also known as Brk) is closely related to the Src family kinases, but lacks a membrane-targeting myristoylation signal. Sublocalization of PTK6 at the plasma membrane enhances its oncogenic potential. To understand the mechanism(s) underlying the oncogenic property of plasma---membrane-associated PTK6, proteins phosphorylated by membrane-targeted myristoylated PTK6 (Myr-PTK6) were enriched and analyzed using a proteomics approach. Eps8 which was identified by this method is phosphorylated by Myr-PTK6 in HEK293 cells. Mouse Eps8 expressed in HEK293 cells is phosphorylated by Myr-PTK6 at residues Tyr497, Tyr524, and Tyr534. Compared to wild-type Eps8 (Eps8 WT), the phosphorylation-defective 3YF mutant (Eps8 3YF) reverts the increased proliferation, migration, and phosphorylation of ERK and FAK mediated by Eps8 WT in HEK293 cells overexpressing PTK6. PTK6 knockdown in T-47D breast cancer cells decreased EGF-induced phosphorylation of Eps8. Endogenous PTK6 phosphorylates ectopically expressed Eps8 WT, but not Eps8 3YF mutant, in EGF-stimulated T-47D cells. The EGF-induced Eps8 phosphorylation enhances activation of ERK and FAK, cell adhesion, and anchorage-independent colony formation in T-47D cells, but not in the PTK6-knokdown T-47D cells. These results indicate that plasma-membrane-associated PTK6 phosphorylates Eps8, which promotes cell proliferation, adhesion, and migration and, thus, tumorigenesis. J. Cell. Biochem. 118: 2887-2895, 2017.

KEYWORDS:

EPS8; MIGRATION; PROLIFERATION; PTK6; TUMORIGENESIS

PMID:
28214294
DOI:
10.1002/jcb.25939
[Indexed for MEDLINE]

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