Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 24 April 1998:
Vol. 280. no. 5363, pp. 599 - 602
DOI: 10.1126/science.280.5363.599
Prev | Table of Contents | Next

Reports

Activation of the Protein Kinase p38 in the Spindle Assembly Checkpoint and Mitotic Arrest

Katsuya Takenaka, Tetsuo Moriguchi, Eisuke Nishida *

The mitogen-activated protein kinase (MAPK) superfamily comprises classical MAPK (also called ERK), c-Jun amino-terminal or stress-activated protein kinase (JNK or SAPK), and p38. Although MAPK is essential for meiotic processes in Xenopus oocytes and the spindle assembly checkpoint in Xenopus egg extracts, the role of members of the MAPK superfamily in M phase or the spindle assembly checkpoint during somatic cell cycles has not been elucidated. The kinase p38, but not MAPK or JNK, was activated in mammalian cultured cells when the cells were arrested in M phase by disruption of the spindle with nocodazole. Addition of activated recombinant p38 to Xenopus cell-free extracts caused arrest of the extracts in M phase, and injection of activated p38 into cleaving embryos induced mitotic arrest. Treatment of NIH 3T3 cells with a specific inhibitor of p38 suppressed activation of the checkpoint by nocodazole. Thus, p38 functions as a component of the spindle assembly checkpoint in somatic cell cycles.

Department of Biophysics, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwake, Sakyo-ku, Kyoto 606-01, Japan.
*   To whom correspondence should be addressed. E-mail: L50174{at}sakura.kudpc.kyoto-u.ac.jp

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Glycogen synthase kinase 3B in bovine oocytes and granulosa cells: possible involvement in meiosis during in vitro maturation.
S. Uzbekova, M. Salhab, C. Perreau, P. Mermillod, and J. Dupont (2008)
Reproduction 138, 235-246
   Abstract »    Full Text »    PDF »
Centrosome separation driven by actin-microfilaments during mitosis is mediated by centrosome-associated tyrosine-phosphorylated cortactin.
W. Wang, L. Chen, Y. Ding, J. Jin, and K. Liao (2008)
J. Cell Sci. 121, 1334-1343
   Abstract »    Full Text »    PDF »
Cell Cycle Synchrony in Giardia intestinalis Cultures Achieved by Using Nocodazole and Aphidicolin.
M. K. Poxleitner, S. C. Dawson, and W. Z. Cande (2008)
Eukaryot. Cell 7, 569-574
   Abstract »    Full Text »    PDF »
p38 Mitogen-Activated Protein Kinase Inhibition Ameliorates Angiotensin II-Induced Target Organ Damage.
J.-K. Park, R. Fischer, R. Dechend, E. Shagdarsuren, A. Gapeljuk, M. Wellner, S. Meiners, P. Gratze, N. Al-Saadi, S. Feldt, et al. (2007)
Hypertension 49, 481-489
   Abstract »    Full Text »    PDF »
Extracellular Signal-regulated Kinase 1/2 Activity Is Not Required in Mammalian Cells during Late G2 for Timely Entry into or Exit from Mitosis.
M. Shinohara, A. V. Mikhailov, J. A. Aguirre-Ghiso, and C. L. Rieder (2006)
Mol. Biol. Cell 17, 5227-5240
   Abstract »    Full Text »    PDF »
Regulation of mitotic function of Chk1 through phosphorylation at novel sites by cyclin-dependent kinase 1 (Cdk1)..
T. Shiromizu, H. Goto, Y. Tomono, J. Bartek, G. Totsukawa, A. Inoko, M. Nakanishi, F. Matsumura, and M. Inagaki (2006)
Genes Cells 11, 477-485
   Abstract »    Full Text »    PDF »
ERK1c regulates Golgi fragmentation during mitosis..
Y. D. Shaul and R. Seger (2006)
J. Cell Biol. 172, 885-897
   Abstract »    Full Text »    PDF »
Brd4 Is Required for Recovery from Antimicrotubule Drug-induced Mitotic Arrest: Preservation of Acetylated Chromatin.
A. Nishiyama, A. Dey, J.-i. Miyazaki, and K. Ozato (2006)
Mol. Biol. Cell 17, 814-823
   Abstract »    Full Text »    PDF »
Selenomethionine induces sustained ERK phosphorylation leading to cell-cycle arrest in human colon cancer cells.
A.-C. Goulet, M. Chigbrow, P. Frisk, and M. A. Nelson (2005)
Carcinogenesis 26, 109-117
   Abstract »    Full Text »    PDF »
Serine-threonine kinases and transcription factors active in signal transduction are detected at high levels of phosphorylation during mitosis in preimplantation embryos and trophoblast stem cells.
J. Liu, E. E Puscheck, F. Wang, A. Trostinskaia, D. Barisic, G. Maniere, D. Wygle, W Zhong, E. H H M Rings, and D. A Rappolee (2004)
Reproduction 128, 643-654
   Abstract »    Full Text »    PDF »
Delayed Hepatocellular Mitotic Progression and Impaired Liver Regeneration in Early Growth Response-1-deficient Mice.
Y. Liao, O. N. Shikapwashya, E. Shteyer, B. K. Dieckgraefe, P. W. Hruz, and D. A. Rudnick (2004)
J. Biol. Chem. 279, 43107-43116
   Abstract »    Full Text »    PDF »
Inhibition of JNK2 Disrupts Anaphase and Produces Aneuploidy in Mammalian Cells.
R. A. MacCorkle and T.-H. Tan (2004)
J. Biol. Chem. 279, 40112-40121
   Abstract »    Full Text »    PDF »
Topoisomerase II and histone deacetylase inhibitors delay the G2/M transition by triggering the p38 MAPK checkpoint pathway.
A. Mikhailov, M. Shinohara, and C. L. Rieder (2004)
J. Cell Biol. 166, 517-526
   Abstract »    Full Text »    PDF »
Chfr acts with the p38 stress kinases to block entry to mitosis in mammalian cells.
T. Matsusaka and J. Pines (2004)
J. Cell Biol. 166, 507-516
   Abstract »    Full Text »    PDF »
Human SAD1 Kinase Is Involved in UV-induced DNA Damage Checkpoint Function.
R. Lu, H. Niida, and M. Nakanishi (2004)
J. Biol. Chem. 279, 31164-31170
   Abstract »    Full Text »    PDF »
Mitotic Regulation of Ribosomal S6 Kinase 1 Involves Ser/Thr, Pro Phosphorylation of Consensus and Non-consensus Sites by Cdc2.
O. J. Shah, S. Ghosh, and T. Hunter (2003)
J. Biol. Chem. 278, 16433-16442
   Abstract »    Full Text »    PDF »
NQK1/NtMEK1 is a MAPKK that acts in the NPK1 MAPKKK-mediated MAPK cascade and is required for plant cytokinesis.
T. Soyano, R. Nishihama, K. Morikiyo, M. Ishikawa, and Y. Machida (2003)
Genes & Dev. 17, 1055-1067
   Abstract »    Full Text »    PDF »
ERKMAPK Activity as a Determinant of Tumor Growth and Dormancy; Regulation by p38SAPK.
J. A. Aguirre-Ghiso, Y. Estrada, D. Liu, and L. Ossowski (2003)
Cancer Res. 63, 1684-1695
   Abstract »    Full Text »    PDF »
Fibronectin- and protein kinase C-mediated activation of ERK/MAPK are essential for proplateletlike formation.
F. Jiang, Y. Jia, and I. Cohen (2002)
Blood 99, 3579-3584
   Abstract »    Full Text »    PDF »
Characterization of the in Vivo Sites of Serine Phosphorylation on Lck Identifying Serine 59 as a Site of Mitotic Phosphorylation.
K. P. Kesavan, C. C. Isaacson, C. L. Ashendel, R. L. Geahlen, and M. L. Harrison (2002)
J. Biol. Chem. 277, 14666-14673
   Abstract »    Full Text »    PDF »
Activation of the p38 Mitogen-activated Protein Kinase Mediates the Suppressive Effects of Type I Interferons and Transforming Growth Factor-beta on Normal Hematopoiesis.
A. Verma, D. K. Deb, A. Sassano, S. Uddin, J. Varga, A. Wickrema, and L. C. Platanias (2002)
J. Biol. Chem. 277, 7726-7735
   Abstract »    Full Text »    PDF »
Hepatitis B Virus X Protein Differentially Regulates Cell Cycle Progression in X-transforming Versus Nontransforming Hepatocyte (AML12) Cell Lines.
S. Lee, C. Tarn, W.-H. Wang, S. Chen, R. L. Hullinger, and O. M. Andrisani (2002)
J. Biol. Chem. 277, 8730-8740
   Abstract »    Full Text »    PDF »
Abnormal Migration Phenotype of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2-/- Neutrophils in Zigmond Chambers Containing Formyl-Methionyl-Leucyl-Phenylalanine Gradients.
M. O. Hannigan, L. Zhan, Y. Ai, A. Kotlyarov, M. Gaestel, and C.-K. Huang (2001)
J. Immunol. 167, 3953-3961
   Abstract »    Full Text »    PDF »
Urokinase Receptor and Fibronectin Regulate the ERKMAPK to p38MAPK Activity Ratios That Determine Carcinoma Cell Proliferation or Dormancy In Vivo.
J. A. Aguirre-Ghiso, D. Liu, A. Mignatti, K. Kovalski, and L. Ossowski (2001)
Mol. Biol. Cell 12, 863-879
   Abstract »    Full Text »
The NPK1 mitogen-activated protein kinase kinase kinase is a regulator of cell-plate formation in plant cytokinesis.
R. Nishihama, M. Ishikawa, S. Araki, T. Soyano, T. Asada, and Y. Machida (2001)
Genes & Dev. 15, 352-363
   Abstract »    Full Text »
Cell cycle roles for two 14-3-3 proteins during Drosophila development.
T. T. Su, D. H. Parry, B. Donahoe, C.-T. Chien, P. H. O'Farrell, and A. Purdy (2001)
J. Cell Sci. 114, 3445-3454
   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 »
Mitogen-Activated Protein Kinases Mediate Matrix Metalloproteinase-9 Expression in Vascular Smooth Muscle Cells.
A. Cho, J. Graves, and M. A. Reidy (2000)
Arterioscler. Thromb. Vasc. Biol. 20, 2527-2532
   Abstract »    Full Text »    PDF »
Control of the eukaryotic cell cycle by MAP kinase signaling pathways.
M. G. WILKINSON and J. B. A. MILLAR (2000)
FASEB J 14, 2147-2157
   Abstract »    Full Text »
Involvement of the MKK6-p38gamma Cascade in gamma -Radiation-Induced Cell Cycle Arrest.
X. Wang, C. H. McGowan, M. Zhao, L. He, J. S. Downey, C. Fearns, Y. Wang, S. Huang, and J. Han (2000)
Mol. Cell. Biol. 20, 4543-4552
   Abstract »    Full Text »
Involvement of p38 Mitogen-Activated Protein Kinase Activation in Bromocriptine-Induced Apoptosis in Rat Pituitary GH3 Cells.
H. Kanasaki, K. Fukunaga, K. Takahashi, K. Miyazaki, and E. Miyamoto (2000)
Biol Reprod 62, 1486-1494
   Abstract »    Full Text »
From the Cover: Functional analysis of oxidative stress-activated mitogen-activated protein kinase cascade in plants.
Y. Kovtun, W.-L. Chiu, G. Tena, and J. Sheen (2000)
PNAS 97, 2940-2945
   Abstract »    Full Text »    PDF »
Activation of the p38 Mitogen-activated Protein Kinase Pathway Arrests Cell Cycle Progression and Differentiation of Immature Thymocytes In Vivo.
N. L. Diehl, H. Enslen, K. A. Fortner, C. Merritt, N. Stetson, C. Charland, R. A. Flavell, R. J. Davis, and M. Rincon (2000)
J. Exp. Med. 191, 321-334
   Abstract »    Full Text »    PDF »
BCL-2 Is Phosphorylated and Inactivated by an ASK1/Jun N-Terminal Protein Kinase Pathway Normally Activated at G2/M.
K. Yamamoto, H. Ichijo, and S. J. Korsmeyer (1999)
Mol. Cell. Biol. 19, 8469-8478
   Abstract »    Full Text »    PDF »
Roles for Basal and Stimulated p21Cip-1/WAF1/MDA6 Expression and Mitogen-activated Protein Kinase Signaling in Radiation-induced Cell Cycle Checkpoint Control in Carcinoma Cells.
J.-S. Park, S. Carter, D. B. Reardon, R. Schmidt-Ullrich, P. Dent, and P. B. Fisher (1999)
Mol. Biol. Cell 10, 4231-4246
   Abstract »    Full Text »
BUBR1 Phosphorylation Is Regulated during Mitotic Checkpoint Activation.
W. Li, Z. Lan, H. Wu, S. Wu, J. Meadows, J. Chen, V. Zhu, and W. Dai (1999)
Cell Growth Differ. 10, 769-775
   Abstract »    Full Text »
Distinct, Constitutively Active MAPK Phosphatases Function in Xenopus Oocytes: Implications for p42 MAPK Regulation In Vivo.
M. L. Sohaskey and J. E. Ferrell Jr. (1999)
Mol. Biol. Cell 10, 3729-3743
   Abstract »    Full Text »
Sensitization of Tumor Cells to Ribotoxic Stress-induced Apoptotic Cell Death: A New Therapeutic Strategy.
S. Ruller, C. Stahl, G. Kohler, B. Eickhoff, J. Breder, M. Schlaak, and J. van der Bosch (1999)
Clin. Cancer Res. 5, 2714-2725
   Abstract »    Full Text »    PDF »
Mitogen-Activated Protein Kinases: Specific Messages from Ubiquitous Messengers.
H. J. Schaeffer and M. J. Weber (1999)
Mol. Cell. Biol. 19, 2435-2444
   Full Text »    PDF »
A MAP Kinase Is Activated Late in Plant Mitosis and Becomes Localized to the Plane of Cell Division.
L. Bögre, O. Calderini, P. Binarova, M. Mattauch, S. Till, S. Kiegerl, C. Jonak, C. Pollaschek, P. Barker, N. S. Huskisson, et al. (1999)
PLANT CELL 11, 101-114
   Abstract »    Full Text »
Requirement for MAPK Activation for Normal Mitotic Progression in Xenopus Egg Extracts.
T. M. Guadagno and J. E. Ferrell Jr. (1998)
Science 282, 1312-1315
   Abstract »    Full Text »
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.
P. S. Shapiro, E. Vaisberg, A. J. Hunt, N. S. Tolwinski, A. M. Whalen, J. R. McIntosh, and N. G. Ahn (1998)
J. Cell Biol. 142, 1533-1545
   Abstract »    Full Text »    PDF »
Active MAP Kinase in Mitosis: Localization at Kinetochores and Association with the Motor Protein CENP-E.
M. Zecevic, A. D. Catling, S. T. Eblen, L. Renzi, J. C. Hittle, T. J. Yen, G. J. Gorbsky, and M. J. Weber (1998)
J. Cell Biol. 142, 1547-1558
   Abstract »    Full Text »    PDF »
Selective Activation of p38 MAPK Cascade and Mitotic Arrest Caused by Low Level Oxidative Stress.
S.-i. Kurata (2000)
J. Biol. Chem. 275, 23413-23416
   Abstract »    Full Text »    PDF »
Stress-induced Activation of Protein Kinase CK2 by Direct Interaction with p38 Mitogen-activated Protein Kinase.
M. Sayed, S. O. Kim, B. S. Salh, O.-G. Issinger, and S. L. Pelech (2000)
J. Biol. Chem. 275, 16569-16573
   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 »
Regulation of the Meiosis-inhibited Protein Kinase, a p38MAPK Isoform, During Meiosis and Following Fertilization of Seastar Oocytes.
D. L. Morrison, A. Yee, H. B. Paddon, D. Vilimek, R. Aebersold, and S. L. Pelech (2000)
J. Biol. Chem. 275, 34236-34244
   Abstract »    Full Text »    PDF »
Growth Regulation via p38 Mitogen-activated Protein Kinase in Developing Liver.
M. M. Awad, H. Enslen, J. M. Boylan, R. J. Davis, and P. A. Gruppuso (2000)
J. Biol. Chem. 275, 38716-38721
   Abstract »    Full Text »    PDF »
p38 Mitogen-activated Protein Kinase-independent Induction of gadd45 Expression in Nerve Growth Factor-induced Apoptosis in Medulloblastomas.
T. T. Chou, J. Q. Trojanowski, and V. M.-Y. Lee (2001)
J. Biol. Chem. 276, 41120-41127
   Abstract »    Full Text »    PDF »
p38 MAP kinase negatively regulates endothelial cell survival, proliferation, and differentiation in FGF-2-stimulated angiogenesis.
T. Matsumoto, I. Turesson, M. Book, P. Gerwins, and L. Claesson-Welsh (2002)
J. Cell Biol. 156, 149-160
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)