5X3S

Crystal structure of mouse Plk1-PBD in complex with phosphopeptide from HEF1 (799-809)

Summary for 5X3S

• Entry DOI: 10.2210/pdb5x3s/pdb
• Descriptor: Serine/threonine-protein kinase PLK1, Peptide from Enhancer of filamentation 1 (3 entities in total)
• Functional Keywords: polo like kinase 1, plk1, polo-box domain, hef1, transferase, transferase-peptide complex, transferase/peptide
• Biological source: Mus musculus (Mouse); More
• Cellular location: Nucleus : Q07832; Cytoplasm, cell cortex. Enhancer of filamentation 1 p55: Cytoplasm, cytoskeleton, spindle: Q14511
• Total number of polymer chains: 4
• Total formula weight: 54477.71

Authors

Kim, J.H.,Shin, S.C.,Kim, E.E. (deposition date: 2017-02-07, release date: 2017-12-20, Last modification date: 2024-11-06)

Primary citation

Lee, K.H.,Hwang, J.A.,Kim, S.O.,Kim, J.H.,Shin, S.C.,Kim, E.E.,Lee, K.S.,Rhee, K.,Jeon, B.H.,Bang, J.K.,Cha-Molstad, H.,Soung, N.K.,Jang, J.H.,Ko, S.K.,Lee, H.G.,Ahn, J.S.,Kwon, Y.T.,Kim, B.Y.
Phosphorylation of human enhancer filamentation 1 (HEF1) stimulates interaction with Polo-like kinase 1 leading to HEF1 localization to focal adhesions.
J. Biol. Chem., 293:847-862, 2018

PubMed 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 1δ (CK1δ) 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.

PubMed: 29191835
DOI: 10.1074/jbc.M117.802587

Experimental method

X-RAY DIFFRACTION (2.899 Å)