Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Oncogene
2014 May 01;3318:2385-94. doi: 10.1038/onc.2013.182.
Show Gene links
Show Anatomy links
RSK promotes G2/M transition through activating phosphorylation of Cdc25A and Cdc25B.
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
.
???displayArticle.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.
Abbott,
Mitogen-activated protein kinase kinase 2 activation is essential for progression through the G2/M checkpoint arrest in cells exposed to ionizing radiation.
1999, Pubmed
Abbott,
Mitogen-activated protein kinase kinase 2 activation is essential for progression through the G2/M checkpoint arrest in cells exposed to ionizing radiation.
1999,
Pubmed
Alvarez,
Pro-Leu-Ser/Thr-Pro is a consensus primary sequence for substrate protein phosphorylation. Characterization of the phosphorylation of c-myc and c-jun proteins by an epidermal growth factor receptor threonine 669 protein kinase.
1991,
Pubmed
Anjum,
The RSK family of kinases: emerging roles in cellular signalling.
2008,
Pubmed
Aressy,
Moderate variations in CDC25B protein levels modulate the response to DNA damaging agents.
2008,
Pubmed
Aressy,
Cell cycle control by the CDC25 phosphatases.
2008,
Pubmed
Bhatt,
Cloning and characterization of Xenopus Rsk2, the predominant p90 Rsk isozyme in oocytes and eggs.
2000,
Pubmed
,
Xenbase
Bouchard,
Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27.
1999,
Pubmed
Boutros,
The when and wheres of CDC25 phosphatases.
2006,
Pubmed
Boutros,
CDC25 phosphatases in cancer cells: key players? Good targets?
2007,
Pubmed
Brown,
Fos family members induce cell cycle entry by activating cyclin D1.
1998,
Pubmed
Cangi,
Constitutive overexpression of CDC25A in primary human mammary epithelial cells results in both defective DNA damage response and chromosomal breaks at fragile sites.
2008,
Pubmed
Carriere,
The RSK factors of activating the Ras/MAPK signaling cascade.
2008,
Pubmed
Castro,
c-Mos and cyclin B/cdc2 connections during Xenopus oocyte maturation.
2001,
Pubmed
,
Xenbase
Cazales,
CDC25B phosphorylation by Aurora-A occurs at the G2/M transition and is inhibited by DNA damage.
2005,
Pubmed
Chen,
The multiple checkpoint functions of CHK1 and CHK2 in maintenance of genome stability.
2008,
Pubmed
Clark,
The serine/threonine protein kinase, p90 ribosomal S6 kinase, is an important regulator of prostate cancer cell proliferation.
2005,
Pubmed
Daksis,
Myc induces cyclin D1 expression in the absence of de novo protein synthesis and links mitogen-stimulated signal transduction to the cell cycle.
1994,
Pubmed
Dalby,
Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible by MAPK.
1998,
Pubmed
Davis,
Monoclonal antibodies to mitotic cells.
1983,
Pubmed
,
Xenbase
Denko,
The human Ha-ras oncogene induces genomic instability in murine fibroblasts within one cell cycle.
1994,
Pubmed
Donzelli,
Regulating mammalian checkpoints through Cdc25 inactivation.
2003,
Pubmed
Dumont,
p90Rsk is not involved in cytostatic factor arrest in mouse oocytes.
2005,
Pubmed
,
Xenbase
Dutertre,
Phosphorylation of CDC25B by Aurora-A at the centrosome contributes to the G2-M transition.
2004,
Pubmed
,
Xenbase
Eisenmann,
Mitogen-activated protein kinase pathway-dependent tumor-specific survival signaling in melanoma cells through inactivation of the proapoptotic protein bad.
2003,
Pubmed
Foijer,
Oncogenic pathways impinging on the G2-restriction point.
2008,
Pubmed
Fox,
Regulation of cyclin D1 and Wnt10b gene expression by cAMP-responsive element-binding protein during early adipogenesis involves differential promoter methylation.
2008,
Pubmed
Gabrielli,
Cdc25 regulates the phosphorylation and activity of the Xenopus cdk2 protein kinase complex.
1992,
Pubmed
,
Xenbase
Gautier,
cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.
1991,
Pubmed
,
Xenbase
Gebauer,
Synthesis and function of Mos: the control switch of vertebrate oocyte meiosis.
1997,
Pubmed
,
Xenbase
Gotoh,
Activation mechanism and function of the MAP kinase cascade.
1995,
Pubmed
,
Xenbase
Harding,
Mechanism of mitosis-specific activation of MEK1.
2003,
Pubmed
,
Xenbase
Hauge,
RSK and MSK in MAP kinase signalling.
2006,
Pubmed
Hermeking,
Identification of CDK4 as a target of c-MYC.
2000,
Pubmed
Kang,
p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells.
2010,
Pubmed
Karlsson,
Cdc25B and Cdc25C differ markedly in their properties as initiators of mitosis.
1999,
Pubmed
Knauf,
Oncogenic RAS induces accelerated transition through G2/M and promotes defects in the G2 DNA damage and mitotic spindle checkpoints.
2006,
Pubmed
Kumagai,
The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system.
1991,
Pubmed
,
Xenbase
Lee,
cdc25+ encodes a protein phosphatase that dephosphorylates p34cdc2.
1992,
Pubmed
,
Xenbase
Lee,
pp60(v-src) induction of cyclin D1 requires collaborative interactions between the extracellular signal-regulated kinase, p38, and Jun kinase pathways. A role for cAMP response element-binding protein and activating transcription factor-2 in pp60(v-src) signaling in breast cancer cells.
1999,
Pubmed
Liu,
The MAP kinase pathway is required for entry into mitosis and cell survival.
2004,
Pubmed
LoPiccolo,
Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations.
2008,
Pubmed
Maller,
OOcyte maturation in amphibians.
1985,
Pubmed
McCubrey,
Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance.
2007,
Pubmed
Moritz,
Akt-RSK-S6 kinase signaling networks activated by oncogenic receptor tyrosine kinases.
2010,
Pubmed
Mueller,
Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15.
1995,
Pubmed
,
Xenbase
Nam,
The ERK-RSK1 activation by growth factors at G2 phase delays cell cycle progression and reduces mitotic aberrations.
2008,
Pubmed
Nurse,
Universal control mechanism regulating onset of M-phase.
1990,
Pubmed
Palmer,
The activation of MAP kinase and p34cdc2/cyclin B during the meiotic maturation of Xenopus oocytes.
2000,
Pubmed
,
Xenbase
Palmer,
A link between MAP kinase and p34(cdc2)/cyclin B during oocyte maturation: p90(rsk) phosphorylates and inactivates the p34(cdc2) inhibitory kinase Myt1.
1998,
Pubmed
,
Xenbase
Pearce,
The nuts and bolts of AGC protein kinases.
2010,
Pubmed
Reinhardt,
Kinases that control the cell cycle in response to DNA damage: Chk1, Chk2, and MK2.
2009,
Pubmed
Rime,
Microinjection of Cdc25 protein phosphatase into Xenopus prophase oocyte activates MPF and arrests meiosis at metaphase I.
1994,
Pubmed
,
Xenbase
Roberts,
Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.
2007,
Pubmed
Roberts,
Distinct cell cycle timing requirements for extracellular signal-regulated kinase and phosphoinositide 3-kinase signaling pathways in somatic cell mitosis.
2002,
Pubmed
Romeo,
Regulation and function of the RSK family of protein kinases.
2012,
Pubmed
Seth,
Signal transduction within the nucleus by mitogen-activated protein kinase.
1992,
Pubmed
Shapiro,
Activation of the MKK/ERK pathway during somatic cell mitosis: direct interactions of active ERK with kinetochores and regulation of the mitotic 3F3/2 phosphoantigen.
1998,
Pubmed
Shaul,
The MEK/ERK cascade: from signaling specificity to diverse functions.
2007,
Pubmed
Tamemoto,
Biphasic activation of two mitogen-activated protein kinases during the cell cycle in mammalian cells.
1992,
Pubmed
Varmeh,
Overexpression of the dual specificity phosphatase, Cdc25C, confers sensitivity on tumor cells to doxorubicin-induced cell death.
2008,
Pubmed
Wang,
Direct roles of the signaling kinase RSK2 in Cdc25C activation during Xenopus oocyte maturation.
2010,
Pubmed
,
Xenbase
Wang,
Regulation of Cdc25C by ERK-MAP kinases during the G2/M transition.
2007,
Pubmed
,
Xenbase
Wright,
Mitogen-activated protein kinase kinase activity is required for the G(2)/M transition of the cell cycle in mammalian fibroblasts.
1999,
Pubmed
Yoon,
The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions.
2006,
Pubmed
