Abstract 5293: GSK3β phosphorylation at serine9 by RSK2 enhances calcium-induced stress tolerance and cell survival

Abstract

Our previous studies demonstrated that RSK2 plays a key role in cell proliferation and transformation induced by tumor promoters such as epidermal growth factor in mouse and human skin cells. However, no direct evidence has been found regarding the relationship between RSK2 and cell survival. In this study, we found that RSK2 interacted and phosphorylated GSK3β at Ser9. Notably, GSK3β phosphorylation at Ser9 was suppressed in RSK2−/− MEFs compared with RSK2+/+ MEFs by stimulation of EGF and calcium ionophore A23187, a cellular calcium stressor. In proliferation, we found that RSK2 deficiency suppressed cell proliferation compared with RSK2+/+ MEFs. In contrast, GSK3β−/− MEFs induced the cell proliferation compared with GSK3β+/+ MEFs. Importantly, RSK2−/− MEFs were induced severe cellular morphology change by A23187 and enhanced G1/G0 and sub-G1 accumulation of the cell cycle phase compared with RSK2+/+ MEFs. The sub-G1 induction in RSK2−/− MEFs by A23187 was correlated with increase of cytochrome c release, caspase-3 cleavage and apoptotic DNA fragmentation compared with RSK2+/+ MEFs. Notably, return back of RSK2 into RSK2−/− MEFs restored A23187-induced morphological change, and decreased apoptosis, apoptotic DNA fragmentation and caspase-3 induction compared with RSK2−/− /mock MEFs. Taken together, our results demonstrated that RSK2 plays an important role in stress-tolerance and cell survival, resulting in cell proliferation and cancer development. Citation Format: Ji-Young Lee, Cheol-Jung Lee, Mee-Hyun Lee, Ji Hong Song, Yong-Yeon Cho. GSK3β phosphorylation at serine9 by RSK2 enhances calcium-induced stress tolerance and cell survival. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5293. doi:10.1158/1538-7445.AM2014-5293