Serine-227 in the N-terminal kinase domain of RSK2 is a potential therapeutic target for mantle cell lymphoma.

ABSTRACT: RSK2 is a serine/threonine kinase downstream signaling mediator in the RAS/ERK signaling pathway and may be a therapeutic target in mantle cell lymphoma (MCL), an almost incurable disease subtype of non-Hodgkin lymphoma. In this study, serine-227 (RSK2^Ser227 ) in the N-terminal kinase domain (NTKD) of RSK2 was found to be ubiquitously active in five MCL-derived cell lines and in tumor tissues derived from five MCL patients. BI-D1870, an inhibitor specific to RSK2-NTKD, caused RSK2^Ser227 dephosphorylation, and thereby, induced dose-dependent growth inhibition via G₂ /M cell cycle blockade and apoptosis in four of the five cell lines, while one cell line showed only modest sensitivity. In addition, RSK2 gene knockdown caused growth inhibition in the four BI-D

SUBMITTER: Matsumura-Kimoto Y 

PROVIDER: S-EPMC7367644 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature