PUBLICATION
PAK4 methylation by the methyltransferase SETD6 attenuates cell adhesion
- Authors
- Vershinin, Z., Feldman, M., Levy, D.
- ID
- ZDB-PUB-210128-30
- Date
- 2020
- Source
- Scientific Reports 10: 17068 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Actin Cytoskeleton/metabolism
- Actin Cytoskeleton/ultrastructure
- Focal Adhesions/genetics
- Focal Adhesions/physiology
- Humans
- Cell Adhesion/genetics
- Cell Adhesion/physiology*
- Zebrafish
- MCF-7 Cells
- Methylation
- beta Catenin/metabolism
- Protein Methyltransferases/genetics
- Protein Methyltransferases/metabolism*
- Recombinant Proteins/chemistry
- Recombinant Proteins/genetics
- Recombinant Proteins/metabolism
- Wnt Signaling Pathway/genetics
- HEK293 Cells
- Mice
- Animals
- Binding Sites/genetics
- Cell Movement/genetics
- Cell Movement/physiology
- Paxillin/metabolism
- Cell Line
- Pseudopodia/metabolism
- Pseudopodia/ultrastructure
- Up-Regulation
- Drosophila melanogaster
- p21-Activated Kinases/chemistry
- p21-Activated Kinases/genetics
- p21-Activated Kinases/metabolism*
- Conserved Sequence
- Amino Acid Sequence
- PubMed
- 33051544 Full text @ Sci. Rep.
Citation
Vershinin, Z., Feldman, M., Levy, D. (2020) PAK4 methylation by the methyltransferase SETD6 attenuates cell adhesion. Scientific Reports. 10:17068.
Abstract
P21-activated kinase 4 (PAK4), a member of serine/threonine kinases family is over-expressed in numerous cancer tumors and is associated with oncogenic cell proliferation, migration and invasion. Our recent work demonstrated that the SET-domain containing protein 6 (SETD6) interacts with and methylates PAK4 at chromatin in mammalian cells, leading to activation of the Wnt/β-catenin signaling pathway. In our current work, we identified lysine 473 (K473) on PAK4 as the primary methylation site by SETD6. Methylation of PAK4 at K473 activates β-catenin transcriptional activity and inhibits cell adhesion. Specific methylation of PAK4 at K473 also attenuates paxillin localization to focal adhesions leading to overall reduction in adhesion-related features, such as filopodia and actin structures. The altered adhesion of the PAK4 wild-type cells is accompanied with a decrease in the migrative and invasive characteristics of the cells. Taken together, our results suggest that methylation of PAK4 at K473 plays a vital role in the regulation of cell adhesion and migration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping