Activation loop phosphorylation of ERK3 is important for its kinase activity and ability to promote lung cancer cell invasiveness

The Journal of Biological Chemistry
Lobna ElkhadragyWeiwen Long

Abstract

ERK3 is an atypical mitogen-activated protein kinase (MAPK) that has recently gained interest for its role in promoting cancer cell migration and invasion. However, the molecular regulation of ERK3 functions in cancer cells is largely unknown. ERK3 has a single phospho-acceptor site (Ser189) in its activation motif rather than the TXY conserved in conventional MAPKs such as ERK1/2. Although dual phosphorylation of the TXY motif is known to be critical for the activation of conventional MAPKs, the role of Ser189 phosphorylation in ERK3 activity and its function in cancer cells remain elusive. 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. Interestingly, a catalytically inactive ERK3 mutant was still capable of increasing migration and invasion, although to a lesser extent compared with WT ERK3, suggesting that ERK3 promotes cancer cell invasiveness by both kinase-dependent and kinase-independent mechanisms. To elucidate how the S189A mutation reduces the invasiveness-promoting ability of ERK3, we tested its effect on the kinase activity o...Continue Reading

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Citations

Apr 22, 2020·ELife·Katarzyna BoguckaKrishnaraj Rajalingam
Jun 16, 2019·International Journal of Molecular Sciences·Monserrat Olea-FloresNapoleón Navarro-Tito
Jan 14, 2020·Bio-protocol·Lobna Elkhadragy, Weiwen Long
Jun 11, 2020·International Journal of Molecular Sciences·Lobna ElkhadragyWeiwen Long
Oct 19, 2020·Cancer Gene Therapy·Katarzyna BoguckaKrishnaraj Rajalingam
Sep 15, 2020·Bioorganic & Medicinal Chemistry Letters·Ulrich GrädlerChristina Esdar
Jan 14, 2022·Experimental & Molecular Medicine·Hyun-Jung AnYong-Yeon Cho

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