In this study, we revealed that activation loop phosphorylation is important for ERK3 in promoting cancer cell invasiveness, as the S189A mutation greatly decreased the ability of ERK3 to promote migration and invasion of lung cancer cells.
We found that in comparison with wild type ERK3, both L290P and L290V mutants have greatly increased activity in promoting cancer cell migration and invasion, but have little impact on ERK3's role in cell proliferation.
Overexpression of p97MAPK was sufficient to inhibit cellular proliferation with concomitant changes in cell cycle regulatory protein expression. p97MAPK also inhibited cancer cell migration and invasion by decreasing Rac1 expression but not that of matrix metalloproteinase 9 which is regulated by other ERKs.