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Science 286 (5443): 1365-1367

Copyright © 1999 by the American Association for the Advancement of Science

Induction of Metaphase Arrest in Cleaving Xenopus Embryos by the Protein Kinase p90Rsk

Stefan D. Gross, Markus S. Schwab, Andrea L. Lewellyn, James L. Maller *

Before fertilization, vertebrate eggs are arrested in metaphase of meiosis II by cytostatic factor (CSF), an activity that requires activation of the mitogen-activated protein kinase (MAPK) pathway. To investigate whether CSF arrest is mediated by the protein kinase p90Rsk, which is phosphorylated and activated by MAPK, a constitutively activated (CA) form of Rsk was expressed in Xenopus embryos. Expression of CA Rsk resulted in cleavage arrest, and cytological analysis showed that arrested blastomeres were in M phase with prominent spindles characteristic of meiotic metaphase. Thus, Rsk appears to be the mediator of MAPK-dependent CSF arrest in vertebrate unfertilized eggs.

Howard Hughes Medical Institute and Department of Pharmacology, University of Colorado School of Medicine, Denver, CO 80262, USA.
*   To whom correspondence should be addressed. E-mail: jim.maller{at}

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E. Hormanseder, T. Tischer, and T. U. Mayer (2013)
EMBO J. 32, 2191-2203
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J. Cell Sci. 126, 1081-1085
   Abstract »    Full Text »    PDF »
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A. L. Illert, M. Zech, C. Moll, C. Albers, S. Kreutmair, C. Peschel, F. Bassermann, and J. Duyster (2012)
J. Biol. Chem. 287, 37997-38005
   Abstract »    Full Text »    PDF »
Pioneering the Xenopus Oocyte and Egg Extract System.
J. L. Maller (2012)
J. Biol. Chem. 287, 21640-21653
   Full Text »    PDF »
Involvement of Polo-like Kinase 1 (Plk1) in Mitotic Arrest by Inhibition of Mitogen-activated Protein Kinase-Extracellular Signal-regulated Kinase-Ribosomal S6 Kinase 1 (MEK-ERK-RSK1) Cascade.
R. Li, D.-F. Chen, R. Zhou, S.-N. Jia, J.-S. Yang, J. S. Clegg, and W.-J. Yang (2012)
J. Biol. Chem. 287, 15923-15934
   Abstract »    Full Text »    PDF »
Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases.
M. Cargnello and P. P. Roux (2011)
Microbiol. Mol. Biol. Rev. 75, 50-83
   Abstract »    Full Text »    PDF »
Dissecting the M Phase-specific Phosphorylation of Serine-Proline or Threonine-Proline Motifs.
C. F. Wu, R. Wang, Q. Liang, J. Liang, W. Li, S. Y. Jung, J. Qin, S. H. Lin, and J. Kuang (2010)
Mol. Biol. Cell 21, 1470-1481
   Abstract »    Full Text »    PDF »
Start of the embryonic cell cycle is dually locked in unfertilized starfish eggs.
M. Hara, M. Mori, T. Wada, K. Tachibana, and T. Kishimoto (2009)
Development 136, 1687-1696
   Abstract »    Full Text »    PDF »
Across the meiotic divide - CSF activity in the post-Emi2/XErp1 era.
J. Q. Wu and S. Kornbluth (2008)
J. Cell Sci. 121, 3509-3514
   Abstract »    Full Text »    PDF »
Involvement of p90 Ribosomal S6 Kinase in Termination of Cell Cycle Arrest during Development of Artemia-encysted Embryos.
J.-Q. Dai, X.-J. Zhu, F.-Q. Liu, J.-H. Xiang, H. Nagasawa, and W.-J. Yang (2008)
J. Biol. Chem. 283, 1705-1712
   Abstract »    Full Text »    PDF »
C/EBP phosphorylation rescues macrophage dysfunction and apoptosis induced by anthrax lethal toxin.
M. Buck and M. Chojkier (2007)
Am J Physiol Cell Physiol 293, C1788-C1796
   Abstract »    Full Text »    PDF »
Control of Emi2 activity and stability through Mos-mediated recruitment of PP2A.
J. Q. Wu, D. V. Hansen, Y. Guo, M. Z. Wang, W. Tang, C. D. Freel, J. J. Tung, P. K. Jackson, and S. Kornbluth (2007)
PNAS 104, 16564-16569
   Abstract »    Full Text »    PDF »
Mouse Emi2 is required to enter meiosis II by reestablishing cyclin B1 during interkinesis.
S. Madgwick, D. V. Hansen, M. Levasseur, P. K. Jackson, and K. T. Jones (2006)
J. Cell Biol. 174, 791-801
   Abstract »    Full Text »    PDF »
p90Rsk is required for G1 phase arrest in unfertilized starfish eggs.
M. Mori, M. Hara, K. Tachibana, and T. Kishimoto (2006)
Development 133, 1823-1830
   Abstract »    Full Text »    PDF »
Cytostatic factor: an activity that puts the cell cycle on hold.
A. Schmidt, N. R. Rauh, E. A. Nigg, and T. U. Mayer (2006)
J. Cell Sci. 119, 1213-1218
   Abstract »    Full Text »    PDF »
Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20.
S. Shoji, N. Yoshida, M. Amanai, M. Ohgishi, T. Fukui, S. Fujimoto, Y. Nakano, E. Kajikawa, and A. C. F. Perry (2006)
EMBO J. 25, 834-845
   Abstract »    Full Text »    PDF »
CaMKII and Polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit.
D. V. Hansen, J. J. Tung, and P. K. Jackson (2006)
PNAS 103, 608-613
   Abstract »    Full Text »    PDF »
Role of p90 Ribosomal S6-Kinase-1 in Oltipraz-Induced Specific Phosphorylation of CCAAT/Enhancer Binding Protein-beta for GSTA2 Gene Transactivation.
S. J. Lee and S. G. Kim (2006)
Mol. Pharmacol. 69, 385-396
   Abstract »    Full Text »    PDF »
Cytoskeleton and cell cycle control during meiotic maturation of the mouse oocyte: integrating time and space.
S. Brunet and B. Maro (2005)
Reproduction 130, 801-811
   Abstract »    Full Text »    PDF »
Mammalian egg activation: from Ca2+ spiking to cell cycle progression.
K. T Jones (2005)
Reproduction 130, 813-823
   Abstract »    Full Text »    PDF »
p90Rsk is not involved in cytostatic factor arrest in mouse oocytes.
J. Dumont, M. Umbhauer, P. Rassinier, A. Hanauer, and M.-H. Verlhac (2005)
J. Cell Biol. 169, 227-231
   Abstract »    Full Text »    PDF »
Functional Characterization of Human RSK4, a New 90-kDa Ribosomal S6 Kinase, Reveals Constitutive Activation in Most Cell Types.
B. A. Dummler, C. Hauge, J. Silber, H. G. Yntema, L. S. Kruse, B. Kofoed, B. A. Hemmings, D. R. Alessi, and M. Frodin (2005)
J. Biol. Chem. 280, 13304-13314
   Abstract »    Full Text »    PDF »
Activation of p90Rsk1 Is Sufficient for Differentiation of PC12 Cells.
E. Silverman, M. Frodin, S. Gammeltoft, and J. L. Maller (2004)
Mol. Cell. Biol. 24, 10573-10583
   Abstract »    Full Text »    PDF »
Functional interaction between p90Rsk2 and Emi1 contributes to the metaphase arrest of mouse oocytes.
M. P. Paronetto, E. Giorda, R. Carsetti, P. Rossi, R. Geremia, and C. Sette (2004)
EMBO J. 23, 4649-4659
   Abstract »    Full Text »    PDF »
Emi1-mediated M-phase arrest in Xenopus eggs is distinct from cytostatic factor arrest.
K. Ohsumi, A. Koyanagi, T. M. Yamamoto, T. Gotoh, and T. Kishimoto (2004)
PNAS 101, 12531-12536
   Abstract »    Full Text »    PDF »
ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions.
P. P. Roux and J. Blenis (2004)
Microbiol. Mol. Biol. Rev. 68, 320-344
   Abstract »    Full Text »    PDF »
Degradation of Polyubiquitinated Cyclin B Is Blocked by the MAPK Pathway at the Metaphase I Arrest in Starfish Oocytes.
E. Oita, K. Harada, and K. Chiba (2004)
J. Biol. Chem. 279, 18633-18640
   Abstract »    Full Text »    PDF »
Protein Kinase C and Mitogen-Activated Protein Kinase Cascade in Mouse Cumulus Cells: Cross Talk and Effect on Meiotic Resumption of Oocyte.
H.-Y. Fan, L.-J. Huo, D.-Y. Chen, H. Schatten, and Q.-Y. Sun (2004)
Biol Reprod 70, 1178-1187
   Abstract »    Full Text »    PDF »
Involvement of Mitogen-Activated Protein Kinase Cascade During Oocyte Maturation and Fertilization in Mammals.
H.-Y. Fan and Q.-Y. Sun (2004)
Biol Reprod 70, 535-547
   Abstract »    Full Text »    PDF »
Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor-mediated metaphase arrest.
B. J. Tunquist, P. A. Eyers, L. G. Chen, A. L. Lewellyn, and J. L. Maller (2003)
J. Cell Biol. 163, 1231-1242
   Abstract »    Full Text »    PDF »
Mitogen-Activated Protein Kinase Pathway-Dependent Tumor-Specific Survival Signaling in Melanoma Cells through Inactivation of the Proapoptotic Protein Bad.
K. M. Eisenmann, M. W. VanBrocklin, N. A. Staffend, S. M. Kitchen, and H.-M. Koo (2003)
Cancer Res. 63, 8330-8337
   Abstract »    Full Text »    PDF »
DOC1R: a MAP kinase substrate that control microtubule organization of metaphase II mouse oocytes.
M. E. Terret, C. Lefebvre, A. Djiane, P. Rassinier, J. Moreau, B. Maro, and M.-H. Verlhac (2003)
Development 130, 5169-5177
   Abstract »    Full Text »    PDF »
Metaphase I arrest of starfish oocytes induced via the MAP kinase pathway is released by an increase of intracellular pH.
K. Harada, E. Oita, and K. Chiba (2003)
Development 130, 4581-4586
   Abstract »    Full Text »    PDF »
Regulation of EDEN-dependent deadenylation of Aurora A/Eg2-derived mRNA via phosphorylation and dephosphorylation in Xenopus laevis egg extracts.
L. Detivaud, G. Pascreau, A. Karaiskou, H. B. Osborne, and J. Z. Kubiak (2003)
J. Cell Sci. 116, 2697-2705
   Abstract »    Full Text »    PDF »
Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggs.
B. J. Tunquist and J. L. Maller (2003)
Genes & Dev. 17, 683-710
   Full Text »    PDF »
pp90RSK- and protein kinase C-dependent pathway regulates p42/44MAPK-induced LDL receptor transcription in HepG2 cells.
G. S. Kapoor, C. Golden, B. Atkins, and K. D. Mehta (2003)
J. Lipid Res. 44, 584-593
   Abstract »    Full Text »    PDF »
Characterization of Ribosomal S6 Protein Kinase p90rsk During Meiotic Maturation and Fertilization in Pig Oocytes: Mitogen-Activated Protein Kinase-Associated Activation and Localization.
H.-Y. Fan, C. Tong, L. Lian, S.-W. Li, W.-X. Gao, Y. Cheng, D.-Y. Chen, H. Schatten, and Q.-Y. Sun (2003)
Biol Reprod 68, 968-977
   Abstract »    Full Text »    PDF »
Phosphorylation of the Cyclin B1 Cytoplasmic Retention Sequence by Mitogen-Activated Protein Kinase and Plx.
S. Walsh, S. S. Margolis, and S. Kornbluth (2003)
Mol. Cancer Res. 1, 280-289
   Abstract »    Full Text »    PDF »
Analyses of Mitogen-Activated Protein Kinase Function in the Maturation of Porcine Oocytes.
S. Ohashi, K. Naito, K. Sugiura, N. Iwamori, S. Goto, H. Naruoka, and H. Tojo (2003)
Biol Reprod 68, 604-609
   Abstract »    Full Text »    PDF »
Mitogen-Activated Protein Kinase in Pfiesteria piscicida and Its Growth Rate-Related Expression.
S. Lin and H. Zhang (2003)
Appl. Envir. Microbiol. 69, 343-349
   Abstract »    Full Text »    PDF »
SNT1/FRS2 Mediates Germinal Vesicle Breakdown Induced by an Activated FGF Receptor1 in Xenopus Oocytes.
K. Mood, R. Friesel, and I. O. Daar (2002)
J. Biol. Chem. 277, 33196-33204
   Abstract »    Full Text »    PDF »
Characterization of the p90 Ribosomal S6 Kinase 2 Carboxyl-terminal Domain as a Protein Kinase.
C. A. Chrestensen and T. W. Sturgill (2002)
J. Biol. Chem. 277, 27733-27741
   Abstract »    Full Text »    PDF »
Mos is not required for the initiation of meiotic maturation in Xenopus oocytes.
A. Dupre, C. Jessus, R. Ozon, and O. Haccard (2002)
EMBO J. 21, 4026-4036
   Abstract »    Full Text »    PDF »
Meiotic spindle stability depends on MAPK-interacting and spindle-stabilizing protein (MISS), a new MAPK substrate.
C. Lefebvre, M. E. Terret, A. Djiane, P. Rassinier, B. Maro, and M.-H. Verlhac (2002)
J. Cell Biol. 157, 603-613
   Abstract »    Full Text »    PDF »
The MAPK pathway triggers activation of Nek2 during chromosome condensation in mouse spermatocytes.
S. Di Agostino, P. Rossi, R. Geremia, and C. Sette (2002)
Development 129, 1715-1727
   Abstract »    Full Text »    PDF »
A Constitutively Active Form of the Protein Kinase p90Rsk1 Is Sufficient to Trigger the G2/M Transition in Xenopus Oocytes.
S. D. Gross, A. L. Lewellyn, and J. L. Maller (2001)
J. Biol. Chem. 276, 46099-46103
   Abstract »    Full Text »    PDF »
Characterization of Regulatory Events Associated with Membrane Targeting of p90 Ribosomal S6 Kinase 1.
S. A. Richards, V. C. Dreisbach, L. O. Murphy, and J. Blenis (2001)
Mol. Cell. Biol. 21, 7470-7480
   Abstract »    Full Text »    PDF »
New B-type cyclin synthesis is required between meiosis I and II during Xenopus oocyte maturation.
H. Hochegger, A. Klotzbucher, J. Kirk, M. Howell, K. le Guellec, K. Fletcher, T. Duncan, M. Sohail, and T. Hunt (2001)
Development 128, 3795-3807
   Abstract »    Full Text »    PDF »
The interplay between cyclin-B-Cdc2 kinase (MPF) and MAP kinase during maturation of oocytes.
A. Abrieu, M. Doree, and D. Fisher (2001)
J. Cell Sci. 114, 257-267
   Abstract »    PDF »
A mammalian oocyte-specific linker histone gene H1oo: homology with the genes for the oocyte-specific cleavage stage histone (cs-H1) of sea urchin and the B4/H1M histone of the frog.
M Tanaka, J. Hennebold, J Macfarlane, and E. Adashi (2001)
Development 128, 655-664
   Abstract »    PDF »
Cloning and Characterization of Xenopus Rsk2, the Predominant p90 Rsk Isozyme in Oocytes and Eggs.
R. R. Bhatt and J. E. Ferrell Jr. (2000)
J. Biol. Chem. 275, 32983-32990
   Abstract »    Full Text »    PDF »
Raf-1/MEK/MAPK Pathway Is Necessary for the G2/M Transition Induced by Nocodazole.
C. Hayne, G. Tzivion, and Z. Luo (2000)
J. Biol. Chem. 275, 31876-31882
   Abstract »    Full Text »    PDF »
A phosphoserine-regulated docking site in the protein kinase RSK2 that recruits and activates PDK1.
M. Frodin, C. J. Jensen, K. Merienne, and S. Gammeltoft (2000)
EMBO J. 19, 2924-2934
   Abstract »    Full Text »    PDF »
SIGNAL TRANSDUCTION:Cell Survival Demands Some Rsk.
A. R. Nebreda and A. Gavin (1999)
Science 286, 1309-1310
   Full Text »
The Protein Kinase p90 Rsk as an Essential Mediator of Cytostatic Factor Activity.
R. R. Bhatt and J. E. Ferrell Jr. (1999)
Science 286, 1362-1365
   Abstract »    Full Text »
Raf-1/MEK/MAPK pathway is necessary for the G2/M transition induced by nocodazole.
C. Hayne, G. Tzivion, and Z. Luo (2000)
J. Biol. Chem.
   Abstract »
Cloning and characterization of Xenopus Rsk2, the predominant p90 Rsk isozyme in oocytes and eggs.
R. R. Bhatt and J. E. Ferrell Jr (2000)
J. Biol. Chem.
   Abstract »

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