title: RSK promotes G2/M transition through activating phosphorylation of Cdc25A and Cdc25B.
abstract: Activation of the mitogen-activated protein kinase (MAPK) cascade in mammalian cell lines positively regulates the G2/M transition. The molecular mechanism underlying this biological phenomenon remains poorly understood. Ribosomal S6 kinase (RSK) is a key downstream element of the MAPK cascade. Our previous studies established roles of RSK2 in Cdc25C activation during progesterone-induced meiotic maturation of Xenopus oocytes. In this study we demonstrate that both recombinant RSK and endogenous RSK in Xenopus egg extracts phosphorylate all three isoforms of human Cdc25 at a conserved motif near the catalytic domain. In human HEK293 and PC-3mm2 cell lines, RSK preferentially phosphorylates Cdc25A and Cdc25B in mitotic cells. Phosphorylation of the RSK sites in these Cdc25 isoforms increases their M-phase-inducing activities. Inhibition of RSK-mediated phosphorylation of Cdc25 inhibits G2/M transition. Moreover, RSK is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of T359/S363 in RSK. Together, these findings indicate that RSK promotes G2/M transition in mammalian cells through activating phosphorylation of Cdc25A and Cdc25B.
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Wu
authors.affiliation: The Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.affiliation: 1] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sun
authors.affiliation: The Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: F
authors.initials: F
authors.lastname: Yin
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Bornmann
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: L-Y
authors.initials: LY
authors.lastname: Yu-Lee
authors.affiliation: 1] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA [2] Department of Genitourinary Medical Oncology Research, David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Gallick
authors.affiliation: The Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 1] Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors.forename: S-H
authors.initials: SH
authors.lastname: Lin
authors.affiliation: 1] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kuang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D059565:G2 Phase Cell Cycle Checkpoints; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009865:Oocytes / Q000201:enzymology; D010766:Phosphorylation; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism*
chemical_list: D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; C517004:CDC25A protein, human; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases