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Lysine methylation signaling regulated by SETD6
Author(s) -
Levy Dan
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.01778
Subject(s) - methylation , lysine , cell adhesion , methyltransferase , focal adhesion , microbiology and biotechnology , chemistry , biochemistry , biology , cell , amino acid , gene
Greater than fifty methyltransferases (PKMTs) are predicted to be present in the human proteome; however, the catalytic activity and substrate specificity for the majority of these enzymes is unknown. Using the protoarray system, we have identified the serine/threonine kinase, PAK4, which is over‐expressed in numerous cancer tumors and is associated with oncogenic cell proliferation, migration and invasion, as a new substrate for methylation by SETD6. 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 structures and actin stress fibers. 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 and represent another example for the importance of lysine methylation in cellular signaling.