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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.
- 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.
- Subjects :
- Amino Acid Sequence
Animals
HEK293 Cells
Humans
Molecular Sequence Data
Oocytes enzymology
Phosphorylation
Ribosomal Protein S6 Kinases, 90-kDa genetics
Xenopus
cdc25 Phosphatases genetics
G2 Phase Cell Cycle Checkpoints
Ribosomal Protein S6 Kinases, 90-kDa metabolism
cdc25 Phosphatases metabolism
Subjects
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