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RSK promotes G2/M transition through activating phosphorylation of Cdc25A and Cdc25B.

RSK promotes G2/M transition through activating phosphorylation of Cdc25A and Cdc25B.

Authors :
Wu CF
Liu S
Lee YC
Wang R
Sun S
Yin F
Bornmann WG
Yu-Lee LY
Gallick GE
Zhang W
Lin SH
Kuang J
Source :
Oncogene [Oncogene] 2014 May 01; Vol. 33 (18), pp. 2385-94. Date of Electronic Publication: 2013 May 27.
Publication Year :
2014

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.

Details

Language :
English
ISSN :
1476-5594
Volume :
33
Issue :
18
Database :
MEDLINE
Journal :
Oncogene
Publication Type :
Academic Journal
Accession number :
23708659
Full Text :
https://doi.org/10.1038/onc.2013.182