Mitogen-activated Protein Kinase (MAPK) Phosphatase 3-mediated Cross-talk between MAPKs ERK2 and p38α
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MAPK phosphatase 3 (MKP3) is highly specific for ERK1/2 inactivation via dephosphorylation of both phosphotyrosine and phosphothreonine critical for enzymatic activation. Here, we show that MKP3 is able to effectively dephosphorylate the phosphotyrosine, but not phosphothreonine, in the activation loop of p38α in vitro and in intact cells. The catalytic constant of the MKP3 reaction for p38α is comparable with that for ERK2. Remarkably, MKP3, ERK2, and phosphorylated p38α can form a stable ternary complex in solution, and the phosphatase activity of MKP3 toward p38α substrate is allosterically regulated by ERK2-MKP3 interaction. This suggests that MKP3 not only controls the activities of ERK2 and p38α but also mediates cross-talk between these two MAPK pathways. The crystal structure of bisphosphorylated p38α has been determined at 2.1 Å resolution. Comparisons between the phosphorylated MAPK structures reveal the molecular basis of MKP3 substrate specificity.
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Despite their high sequence similarity, HePTP, STEP, and PTPSL regulate/deactivate p38 with different efficiencies.
“Despite their high sequence similarity, it has been shown that these three phosphatases regulate/deactivate p38 with different efficiencies.76”
From Molecular basis of MAP kinase regulation (2013) · cites this paper as [76]
Cites
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475 · see citing works
<i>Coot</i> : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571 · see citing works
PROCHECK: a program to check the stereochemical quality of protein structures
Laskowski, R. A., MacArthur, M. W., Moss, D. S., & Thornton, J. M. (1993) · Journal of Applied Crystallography · doi:10.1107/s0021889892009944 · Cited by 24,581 · see citing works
Calcium's Role in Mechanotransduction during Muscle Development
Damm, T. B., & Egli, M. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356667 · Cited by 14,548 · see citing works
<i>PHENIX</i> : building new software for automated crystallographic structure determination
Adams, P. D., Grosse-Kunstleve, R. W., Hung, L.-W., Ioerger, T. R., McCoy, A. J., Moriarty, N. W., Read, R. J., Sacchettini, J. C., Sauter, N. K., & Terwilliger, T. C. (2002) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444902016657 · Cited by 4,361 · see citing works
Mitogen-Activated Protein (MAP) Kinase Pathways: Regulation and Physiological Functions*
Pearson, G. W., Robinson, F. L., Gibson, T. B., Xu, B.-E., Karandikar, M. S., Berman, K. S., & Cobb, M. H. (2001) · Endocrine Reviews · doi:10.1210/edrv.22.2.0428 · Cited by 4,037 · see citing works
Kyriakis, J. M., & Avruch, J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.807 · Cited by 3,369 · see citing works
Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human
Widmann, C., Gibson, S. B., Jarpe, M. B., & Johnson, G. L. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.1.143 · Cited by 2,707 · see citing works
Roux, P. P., & Blenis, J. (2004) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.68.2.320-344.2004 · Cited by 2,494 · see citing works
Signal Transduction through MAP Kinase Cascades
Lewis, T. S., Shapiro, P. S., & Ahn, N. G. (1998) · Advances in cancer research · doi:10.1016/s0065-230x(08)60765-4 · Cited by 1,746 · see citing works
Likelihood-enhanced fast translation functions
McCoy, A. J., Grosse‐Kunstleve, R. W., Storoni, L. C., & Read, R. J. (2005) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444905001617 · Cited by 1,641 · see citing works
Cobb, M. H. (1999) · Progress in Biophysics and Molecular Biology · doi:10.1016/s0079-6107(98)00056-x · Cited by 869 · see citing works
Dual specificity phosphatases: a gene family for control of MAP kinase function
Camps, M., NICHOLS, A., & Arkinstall, S. (2000) · The FASEB Journal · doi:10.1096/fasebj.14.1.6 · Cited by 812 · see citing works
Activation mechanism of the MAP kinase ERK2 by dual phosphorylation
Canagarajah, B. J., Khokhlatchev, A., Cobb, M. H., & Goldsmith, E. J. (1997) · Cell · doi:10.1016/s0092-8674(00)80351-7 · Cited by 729 · see citing works
Webb, M. (1992) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.89.11.4884 · Cited by 540 · see citing works
Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen-activated protein kinase.
Camps, M., Nichols, A., Gilliéron, C., Antonsson, B., Muda, M., Chabert, C., Boschert, U., & Arkinstall, S. (1998) · Science · doi:10.1126/science.280.5367.1262 · Cited by 523 · see citing works
Structure and regulation of MAPK phosphatases
Farooq, A., & Zhou, M. (2004) · Cellular Signalling · doi:10.1016/j.cellsig.2003.12.008 · Cited by 452 · see citing works
Groom, L. A., Sneddon, A. A., Alessi, D. R., Dowd, S., & Keyse, S. M. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00731.x · Cited by 412 · see citing works
Muda, M., Theodosiou, A. M., Rodrigues, N. R., Boschert, U., Camps, M., Gilliéron, C., Davies, K. E., Ashworth, A., & Arkinstall, S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27205 · Cited by 375 · see citing works
Zheng, J., Trafny, E. A., Knighton, D. R., Xuong, N., Taylor, S. S., Eyck, L. F. T., & Sowadski, J. M. (1993) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444993000423 · Cited by 374 · see citing works
Muda, M., Boschert, U., Dickinson, R. J., Martinou, J., Martinou, I., Camps, M., Schlegel, W., & Arkinstall, S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.8.4319 · Cited by 347 · see citing works
Diverse physiological functions for dual-specificity MAP kinase phosphatases
Dickinson, R. J., & Keyse, S. M. (2006) · Journal of Cell Science · doi:10.1242/jcs.03266 · Cited by 329 · see citing works
Docking Motif Interactions in MAP Kinases Revealed by Hydrogen Exchange Mass Spectrometry
Lee, T., Hoofnagle, A. N., Kabuyama, Y., Stroud, J., Min, X., Goldsmith, E. J., Chen, L., Resing, K. A., & Ahn, N. G. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00161-3 · Cited by 282 · see citing works
The structure of mitogen-activated protein kinase p38 at 2.1-Å resolution
Wang, Z., Harkins, P. C., Ulevitch, R. J., Han, J., Cobb, M. H., & Goldsmith, E. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.6.2327 · Cited by 275 · see citing works
Self-citationCrystal Structure of p38 Mitogen-activated Protein Kinase
Wilson, K. P., Fitzgibbon, M. J., Caron, P. R., Griffith, J. P., Chen, W., McCaffrey, P. G., Chambers, S. P., & Su, M. S. S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27696 · Cited by 262 · see citing works
Morphology of protein–protein interfaces
Larsen, T. A., Olson, A. J., & Goodsell, D. S. (1998) · Structure · doi:10.1016/s0969-2126(98)00044-6 · Cited by 228 · see citing works
Molecular Cloning and Characterization of a Novel Dual Specificity Phosphatase, MKP-5
Tanoue, T., Moriguchi, T., & Nishida, E. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.28.19949 · Cited by 225 · see citing works
The Specificity of Extracellular Signal-regulated Kinase 2 Dephosphorylation by Protein Phosphatases
Zhou, B., Wang, Z.-X., Zhao, Y. C., Brautigan, D. L., & Zhang, Z. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203969200 · Cited by 211 · see citing works
Self-citationFantz, D. A., Jacobs, D., Glossip, D., & Kornfeld, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102512200 · Cited by 183 · see citing works
Zhao, Y., & Zhang, Z. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103369200 · Cited by 175 · see citing works
Muda, M., Theodosiou, A. M., Gilliéron, C., Smith, A., Chabert, C., Camps, M., Boschert, U., Rodrigues, N. R., Davies, K. E., Ashworth, A., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.15.9323 · Cited by 154 · see citing works
McDonald, N. Q., Stewart, A., Dowd, S., et al. (1999) · Nature Structural Biology · doi:10.1038/5861 · Cited by 148 · see citing works
Saxena, M., Williams, S., Brockdorff, J. L., Gilman, J., & Mustelin, T. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.17.11693 · Cited by 135 · see citing works
Bellon, S. F., Fitzgibbon, M. J., Fox, T., Hsiao, H.-M., & Wilson, K. P. (1999) · Structure · doi:10.1016/s0969-2126(99)80173-7 · Cited by 133 · see citing works
MUÑOZ, J. J., TÁRREGA, C., BLANCO-APARICIO, C., & PULIDO, R. (2003) · Biochemical Journal · doi:10.1042/bj20021941 · Cited by 121 · see citing works
Solution Structure of ERK2 Binding Domain of MAPK Phosphatase MKP-3
Farooq, A., Chaturvedi, G., Mujtaba, S., Plotnikova, O., Zeng, L., Dhalluin, C., Ashton, R., & Zhou, M.-M. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00186-1 · Cited by 119 · see citing works
Multiple Regions of MAP Kinase Phosphatase 3 Are Involved in Its Recognition and Activation by ERK2
Zhou, B., Wu, L., Shen, K., Zhang, J., Lawrence, D. S., & Zhang, Z. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009753200 · Cited by 116 · see citing works
Mourey, R. J., Vega, Q. C., Campbell, J. S., Wenderoth, M. P., Hauschka, S. D., Krebs, E. G., & Dixon, J. E. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.7.3795 · Cited by 115 · see citing works
Selective Targeting of MAPKs to the ETS Domain Transcription Factor SAP-1
Galanis, Α., Yang, S., & Sharrocks, A. D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007697200 · Cited by 95 · see citing works
Fjeld, C. C., Rice, A. E., Kim, Y., Gee, K. R., & Denu, J. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.10.6749 · Cited by 90 · see citing works
Zhang, Y., Mei, Z., Wu, J., & Wang, Z. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801703200 · Cited by 84 · see citing works
Self-citationPositive crosstalk between ERK and p38 in melanoma stimulates migration and in vivo proliferation
Estrada, Y. D., Dong, J., & Ossowski, L. (2008) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2008.00520.x · Cited by 84 · see citing works
Mechanism of Mitogen-activated Protein Kinase Phosphatase-3 Activation by ERK2
Zhou, B., & Zhang, Z. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.50.35526 · Cited by 69 · see citing works
Mapping ERK2-MKP3 Binding Interfaces by Hydrogen/Deuterium Exchange Mass Spectrometry
Zhou, B., Zhang, J., Liu, S., Reddy, S., Wang, F., & Zhang, Z. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608916200 · Cited by 56 · see citing works
Jeong, D. G., Yoon, T., Kim, J., Shim, M. Y., Jung, S., Son, J. H., Ryu, S. E., & Kim, S. J. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.05.059 · Cited by 45 · see citing works
Purification and Kinetic Characterization of the Mitogen-activated Protein Kinase Phosphatase rVH6
Wiland, A. M., Denu, J. M., Mourey, R. J., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.52.33486 · Cited by 30 · see citing works
Sergienko, E. A., & Srivastava, D. K. (1994) · Analytical Biochemistry · doi:10.1006/abio.1994.1424 · Cited by 28 · see citing works
A Continuous Spectrophotometric Assay for Protein Phosphatases
Cheng, Q., Wang, Z. X., & Killilea, S. D. (1995) · Analytical Biochemistry · doi:10.1006/abio.1995.1192 · Cited by 24 · see citing works
Self-citationKinetic mechanism for p38 MAP kinase α
Szafranska, A. E., & Dalby, K. N. (2005) · FEBS Journal · doi:10.1111/j.1742-4658.2005.04827.x · Cited by 21 · see citing works
Szafranska, A. E., Luo, X., & Dalby, K. N. (2004) · Analytical Biochemistry · doi:10.1016/j.ab.2004.09.039 · Cited by 11 · see citing works
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Dual‐specificity MAP kinase phosphatases (MKPs): Shaping the outcome of MAP kinase signalling
Caunt, C. J., & Keyse, S. M. (2013) · The FEBS Journal · doi:10.1111/j.1742-4658.2012.08716.x · Cited by 535 · see citing works
Molecular basis of MAP kinase regulation
Peti, W., & Page, R. (2013) · Protein Science · doi:10.1002/pro.2374 · Cited by 302 · see citing works
Francis, D. M., Kumar, G. S., Koveal, D., Tortajada, A., Page, R., & Peti, W. (2013) · Structure · doi:10.1016/j.str.2013.07.003 · Cited by 21 · see citing works
NMR Spectroscopic Investigations of the Activated p38α Mitogen‐Activated Protein Kinase
Nielsen, G., & Schwalbe, H. (2011) · ChemBioChem · doi:10.1002/cbic.201100527 · Cited by 15 · see citing works
- Authors
- Zhang, Y.-Y., Wu, J.-W., & Wang, Z.-X.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Wang, Zhi-Xin
- ORCID
- Wang, Zhi-Xin
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 286
- Issue
- 18
- Pages
- 16150-16162
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3091224
- OpenAlex
- W1965902294
- Cited by
- 63
- References
- 50
- Citations by year
- 2026: 7 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 10 · 2013: 6 · 2012: 7
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- MKP-3, ERK2, p38α, dephosphorylation, substrate specificity, allosteric regulation, ternary complex, phosphotyrosine, phosphothreonine
- MeSH terms
- Animals, Humans, Phosphorylation, Substrate Specificity, Protein Structure, Tertiary, Crystallography, X-Ray, Mitogen-Activated Protein Kinase 1, MAP Kinase Signaling System, p38 Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Mice, Dual Specificity Phosphatase 6, HEK293 Cells
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