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Title 

Phosphorylation of human enhancer filamentation 1 (HEF1) stimulates interaction with Polo-like kinase 1 leading to HEF1 localization to focal adhesions

Authors 

Kyung Ho LeeJeong Ah HwangSun-Ok KimJ H KimS C ShinE E KimK S LeeK RheeB H JeonJ K BangHyunjoo Cha-MolstadNak-Kyun SoungJae-Hyuk JangSung-Kyun KoHee Gu LeeJong Seog AhnY T KwonBo Yeon Kim

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

2018

Citation 

Journal of Biological Chemistry

Abstract 

Elevated expression of human enhancer filamentation 1 (HEF1; also known as NEDD9 or Cas-L) is an essential stimulus for the metastatic process of various solid tumors. This process requires HEF1 localization to focal adhesions (FAs). Although the association of HEF1 with FAs is considered to play a role in cancer cell migration, the mechanism targeting HEF1 to FAs remains unclear. Moreover, up-regulation of Polo-like kinase 1 (Plk1) positively correlates with human cancer metastasis, yet how Plk1 deregulation promotes metastasis remains elusive. Here, we report that casein kinase 1 (CK1) phosphorylates HEF1 at Ser-780 and Thr-804 and that these phosphorylation events promote a physical interaction between Plk1 and HEF1. We found that this interaction is critical for HEF1 translocation to FAs and for inducing migration of HeLa cells. Plk1-docking phosphoepitopes were mapped/confirmed in HEF1 by various methods, including X-ray crystallography, and mutated for functional analysis in HeLa cells. In summary, our results reveal the role of a phosphorylation-dependent HEF1?Plk1 complex in HEF1 translocation to FAs to induce cell migration. Our findings provide critical mechanistic insights into the HEF1?Plk1 complex? dependent localization of HEF1 to FAs underlying the metastatic process and may therefore contribute to the development of new cancer therapies

ISSN 

0021-9258

Link 

http://dx.doi.org/10.1074/jbc.M117.802587

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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