The Evolution of the MAP Kinase Pathways: Coduplication of Interacting Proteins Leads to New Signaling Cascades

Caffrey, Daniel R.; O'Neill, Luke A.J.; Shields, Denis C.

doi:10.1007/pl00006578

Cited by 124Protein Kinase Regulation and GTPase SignalingGenomics and Phylogenetic StudiesFungal and yeast genetics research

The Evolution of the MAP Kinase Pathways: Coduplication of Interacting Proteins Leads to New Signaling Cascades

Caffrey, Daniel R., O'Neill, Luke A.J., Shields, Denis C.·1999·Journal of Molecular Evolution

DOI 10.1007/pl00006578

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Abstract

The MAP-kinase pathways are intracellular signaling modules that are likely to exist in all eukaryotes. We provide an evolutionary model for these signaling pathways by focusing on the gene duplications that have occurred since the divergence of animals from yeast. Construction of evolutionary trees with confidence assessed by bootstrap clearly shows that the mammalian JNK and p38 pathways arose from an ancestral hyperosmolarity pathway after the split from yeast and before the split from C. elegans. These coduplications of interacting proteins at the MAPK and MEK levels have since evolved toward substrate specificity, thus giving distinct pathways. Mammalian duplications since the split from C. elegans are often associated with divergent tissue distribution but do not appear to confer detectable substrate specificity. The yeast kinase cascades have undergone similar fundamental functional changes since the split from mammals, with duplications giving rise to central signaling components of the filamentous and hypoosmolarity pathways. Experimentally defined cross-talk between yeast pheromone and hyperosmolarity pathways is mirrored with corresponding cross-talk in mammalian pathways, suggesting the existence of ancient orthologous cross-talk; our analysis of gene duplications at all levels of the cascade is consistent with this model but does not always provide significant bootstrap support. Our data also provide insights at different levels of the cascade where conflicting experimental evidence exists.

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The docking grooves of paralogous MAPKs are highly similar, likely because of duplication events and because ERK2, p38α, and JNK1 share about 40-50% sequence identity.
“The docking grooves of paralogous MAPKs show a high degree of similarity, likely because each major group of MAPKs in animals - typical MAPKs such as extracellular signal-regulated kinase (ERK) 1/2; c-Jun N-terminal kinases (JNKs); p38s; ERK5; and atypical MAPKs such as ERK3, 4, and 7 - emerged through whole genome or individual gene duplication events and because three members of this family - ER”
From Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove (2012) · cites this paper as [11]
MAPKs represent a paradigm for understanding how specificity in cellular signaling can be achieved with enzymes that share a common origin.
“MAPKs represent a paradigm for understanding how specificity in cellular signaling can be achieved with enzymes that share a common origin (11).”
From Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove (2012) · cites this paper as [11]

Basic local alignment search tool
Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990) · Journal of Molecular Biology · doi:10.1006/jmbi.1990.9999 · Cited by 98,669 · see citing works
CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice
Thompson, J. D., Higgins, D. G., & Gibson, T. J. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.22.4673 · Cited by 64,617 · see citing works
The neighbor-joining method: a new method for reconstructing phylogenetic trees.
Saitou, N., & Nei, M. (1987) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a040454 · Cited by 59,962 · see citing works
TGF-β SIGNAL TRANSDUCTION
Massagué, J. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.753 · Cited by 7,571 · see citing works
Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation
Marshall, C. J. (1995) · Cell · doi:10.1016/0092-8674(95)90401-8 · Cited by 4,557 · see citing works
A MAP Kinase Targeted by Endotoxin and Hyperosmolarity in Mammalian Cells
Han, J., Lee, J. D., Bibbs, L., & Ulevitch, R. J. (1994) · Science · doi:10.1126/science.7914033 · Cited by 2,647 · see citing works
Mitogen-activated protein kinase pathways
Robinson, M. J., & Cobb, M. H. (1997) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(97)80061-0 · Cited by 2,495 · see citing works
Induction of Apoptosis by ASK1, a Mammalian MAPKKK That Activates SAPK/JNK and p38 Signaling Pathways
Ichijo, H., Nishida, E., Irie, K., ten Dijke, P., Saitoh, M., Moriguchi, T., Takagi, M., Matsumoto, K., Miyazono, K., & Gotoh, Y. (1997) · Science · doi:10.1126/science.275.5296.90 · Cited by 2,310 · see citing works
Pro-inflammatory Cytokines and Environmental Stress Cause p38 Mitogen-activated Protein Kinase Activation by Dual Phosphorylation on Tyrosine and Threonine
Raingeaud, J., Gupta, S., Rogers, J. S., Dickens, M., Han, J., Ulevitch, R. J., & Davis, R. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7420 · Cited by 2,244 · see citing works
Mammalian Ras interacts directly with the serine/threonine kinase Raf.
Vojtek, A., Hollenberg, S., & Cooper, J. A. (1993) · Cell · doi:10.1016/0092-8674(93)90307-c · Cited by 1,971 · see citing works
CTR1, a negative regulator of the ethylene response pathway in arabidopsis, encodes a member of the Raf family of protein kinases
Kieber, J. J., Rothenberg, M., Roman, G., Feldmann, K. A., & Ecker, J. R. (1993) · Cell · doi:10.1016/0092-8674(93)90119-b · Cited by 1,925 · see citing works
cPLA2 is phosphorylated and activated by MAP kinase
Lin, L., Wartmann, M., Lin, A. Y., Knopf, J. L., Seth, A., & Davis, R. J. (1993) · Cell · doi:10.1016/0092-8674(93)90666-e · Cited by 1,851 · see citing works
Molecular evidence for an ancient duplication of the entire yeast genome
Wolfe, K. H., & Shields, D. C. (1997) · Nature · doi:10.1038/42711 · Cited by 1,785 · see citing works
Self-citation
How MAP Kinases Are Regulated
Cobb, M. H., & Goldsmith, E. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.25.14843 · Cited by 1,718 · see citing works
The small GTP-binding proteins Rac1 and Cdc42regulate the activity of the JNK/SAPK signaling pathway
Coso, O. A., Chiariello, M., Yu, J., Teramoto, H., Crespo, P., Xu, N., Miki, T., & Gutkind, J. S. (1995) · Cell · doi:10.1016/s0092-8674(05)80018-2 · Cited by 1,629 · see citing works
Independent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms
Dérijard, B., Raingeaud, J., Barrett, T., Wu, I.-H., Han, J., Ulevitch, R. J., & Davis, R. J. (1995) · Science · doi:10.1126/science.7839144 · Cited by 1,555 · see citing works
Selective activation of the JNK signaling cascadeand c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs
Minden, A., Lin, A., Claret, F.-X., Abo, A., & Karin, M. (1995) · Cell · doi:10.1016/s0092-8674(05)80019-4 · Cited by 1,481 · see citing works
Three-dimensional structure of the tyrosine kinase c-Src
Xu, W., Harrison, S. C., & Eck, M. J. (1997) · Nature · doi:10.1038/385595a0 · Cited by 1,428 · see citing works
Identification of a Member of the MAPKKK Family as a Potential Mediator of TGF-β Signal Transduction
Yamaguchi, T., Shirakabe, K., Shibuyà, H., Irie, K., Oishi, I., Ueno, N., Taniguchi, T., Nishida, E., & Matsumoto, K. (1995) · Science · doi:10.1126/science.270.5244.2008 · Cited by 1,344 · see citing works
Regulation of transcription by MAP kinase cascades
Treisman, R. (1996) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(96)80067-6 · Cited by 1,296 · see citing works
MAP3K-related kinase involved in NF-KB induction by TNF, CD95 and IL-1
Malinin, N. L., Boldin, M., Kovalenko, A. V., & Wallach, D. (1997) · Nature · doi:10.1038/385540a0 · Cited by 1,279 · see citing works
Protein kinase Cα activates RAF-1 by direct phosphorylation
Kölch, W., Heidecker, G., Kochs, G., Hummel, R., Vahidi, H., Mischak, H., Finkenzeller, G., Marmé, D., & Rapp, U. R. (1993) · Nature · doi:10.1038/364249a0 · Cited by 1,278 · see citing works
[2] Protein kinase catalytic domain sequence database: Identification of conserved features of primary structure and classification of family members
Hanks, S. K., & Quinn, A. M. (1991) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(91)00126-h · Cited by 1,232 · see citing works
CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF THE HUMAN INSULIN RECEPTOR
Hubbard, S. R., Wei, L., Ellis, L., & Hendrickson, W. A. (1994) · Nature · doi:10.1038/372746a0 · Cited by 1,080 · see citing works
Differential Activation of ERK and JNK Mitogen-Activated Protein Kinases by Raf-1 and MEKK
Minden, A., Lin, A., McMahon, M., Lange, C. A., Dérijard, B., Davis, R. J., Johnson, G. L., & Karin, M. (1994) · Science · doi:10.1126/science.7992057 · Cited by 1,069 · see citing works
A Divergence in the MAP Kinase Regulatory Network Defined by MEK Kinase and Raf
Lange, C. A., Pleiman, C., Gardner, A. M., Blumer, K., & Johnson, G. L. (1993) · Science · doi:10.1126/science.8385802 · Cited by 1,059 · see citing works
MAP kinase pathways in yeast: For mating and more
Herskowitz, I. (1995) · Cell · doi:10.1016/0092-8674(95)90402-6 · Cited by 1,007 · see citing works
Crystal structure of cyclin-dependent kinase 2
Bondt, H. L. D., Rosenblatt, J., Jancarik, J., Jones, H. D., Morgan, D. O., & Kim, S. (1993) · Nature · doi:10.1038/363595a0 · Cited by 980 · see citing works
Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun
Sánchez, I., Hughes, R. T., Mayer, B. J., Yee, K. O., Woodgett, J. R., Avruch, J., Kyriakls, J. M., & Zon, L. I. (1994) · Nature · doi:10.1038/372794a0 · Cited by 970 · see citing works
Identification of a Dual Specificity Kinase That Activates the Jun Kinases and p38-Mpk2
Lin, A., Minden, A., Martinetto, H., Claret, F.-X., Lange, C. A., Mercurio, F., Johnson, G. L., & Karin, M. (1995) · Science · doi:10.1126/science.7716521 · Cited by 763 · see citing works
Characterization of the Structure and Function of a New Mitogen-activated Protein Kinase (p38β)
Jiang, Y., Chen, C., Li, Z., Guo, W., Gegner, J. A., Lin, S., & Han, J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.30.17920 · Cited by 746 · see citing works
Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro
Warne, P. H., Vician, P. R., & Downward, J. (1993) · Nature · doi:10.1038/364352a0 · Cited by 729 · see citing works
Rho Family GTPases Regulate p38 Mitogen-activated Protein Kinase through the Downstream Mediator Pak1
Zhang, S., Han, J., Sells, M. A., Chernoff, J., Knaus, U. G., Ulevitch, R. J., & Bokoch, G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.41.23934 · Cited by 726 · see citing works
Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1
Yan, M., Dai, T., Deak, J. C., Kyriakis, J. M., Zon, L. I., Woodgett, J. R., & Templeton, D. J. (1994) · Nature · doi:10.1038/372798a0 · Cited by 705 · see citing works
Monophyletic Origins of the Metazoa: an Evolutionary Link with Fungi
Wainright, P. O., Hinkle, G., Sogin, M. L., & Stickel, S. K. (1993) · Science · doi:10.1126/science.8469985 · Cited by 653 · see citing works
A Mammalian Scaffold Complex That Selectively Mediates MAP Kinase Activation
Whitmarsh, A. J., Cavanagh, J., Tournier, C., Yasuda, J., & Davis, R. J. (1998) · Science · doi:10.1126/science.281.5383.1671 · Cited by 652 · see citing works
Atomic structure of the MAP kinase ERK2 at 2.3 A resolution
Zhang, F., Strand, A., Robbins, D., Cobb, M. H., & Goldsmith, E. J. (1994) · Nature · doi:10.1038/367704a0 · Cited by 592 · see citing works
Crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with magnesium-ATP and peptide inhibitor
Zheng, J., Knighton, D. R., Eyck, L. F. T., Karlsson, R., Xuong, N., Taylor, S. S., & Sowadski, J. M. (1993) · Biochemistry · doi:10.1021/bi00060a005 · Cited by 590 · see citing works
BMK1/ERK5 regulates serum‐induced early gene expression through transcription factor MEF2C
Kato, Y., Kravchenko, V. V., Tapping, R. I., Han, J., Ulevitch, R. J., & Lee, J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.23.7054 · Cited by 582 · see citing works
An Osmosensing Signal Transduction Pathway in Mammalian Cells
Galcheva-Gargova, Z., Dérijard, B., Wu, I., & Davis, R. J. (1994) · Science · doi:10.1126/science.8047888 · Cited by 569 · see citing works
Osmotic Activation of the HOG MAPK Pathway via Ste11p MAPKKK: Scaffold Role of Pbs2p MAPKK
Posas, F., & Saito, H. (1997) · Science · doi:10.1126/science.276.5319.1702 · Cited by 565 · see citing works
Selective Activation of p38 Mitogen-activated Protein (MAP) Kinase Isoforms by the MAP Kinase Kinases MKK3 and MKK6
Enslen, H., Raingeaud, J., & Davis, R. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.3.1741 · Cited by 534 · see citing works
Characterization of the Structure and Function of the Fourth Member of p38 Group Mitogen-activated Protein Kinases, p38δ
Jiang, Y., Gram, H., Zhao, M. F., New, L., Gu, J., Feng, L., Padova, F. D., Ulevitch, R. J., & Han, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.48.30122 · Cited by 489 · see citing works
MP1: A MEK Binding Partner That Enhances Enzymatic Activation of the MAP Kinase Cascade
Schaeffer, H. J., Catling, A. D., Eblen, S. T., Collier, L. S., Krauss, A., & Weber, M. J. (1998) · Science · doi:10.1126/science.281.5383.1668 · Cited by 472 · see citing works
Transcriptional regulation by MAP kinases
Davis, R. (1995) · Molecular Reproduction and Development · doi:10.1002/mrd.1080420414 · Cited by 450 · see citing works
The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338
King, A. J., Sun, H., Diaz, B., Barnard, D., Miao, W., Bagrodia, S., & Marshall, M. S. (1998) · Nature · doi:10.1038/24184 · Cited by 443 · see citing works
Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor
Kato, Y., Tapping, R. I., Huang, S., Watson, M. H., Ulevitch, R. J., & Lee, J.-D. (1998) · Nature · doi:10.1038/27234 · Cited by 439 · see citing works
Rac Regulation of Transformation, Gene Expression, and Actin Organization by Multiple, PAK-Independent Pathways
Westwick, J. K., Lambert, Q. T., Clark, G. J., Symons, M. H., Aelst, L. V., Pestell, R. G., & Der, C. J. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.3.1324 · Cited by 436 · see citing works
The protein kinase homologue Ste20p is required to link the yeast pheromone response G‐protein beta gamma subunits to downstream signalling components.
Leberer, E., Dignard, D., Harcus, D., Thomas, D. Y., & Whiteway, M. S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05587.x · Cited by 432 · see citing works
Activation of the novel stress‐activated protein kinase SAPK4 by cytokines and cellular stresses is mediated by SKK3 (MKK6); comparison of its substrate specificity with that of other SAP kinases
Goedert, M., Cuenda, A., Craxton, M., Jakes, R., & Cohen, P. (1997) · The EMBO Journal · doi:10.1093/emboj/16.12.3563 · Cited by 420 · see citing works
Cross‐cascade activation of ERKs and ternary complex factors by Rho family proteins
Frost, J. A., Steen, H., Shapiro, P. S., Lewis, T., Ahn, N. G., Shaw, P. E., & Cobb, M. H. (1997) · The EMBO Journal · doi:10.1093/emboj/16.21.6426 · Cited by 414 · see citing works
Regulation of Human Leukocyte p21-Activated Kinases Through G Protein—Coupled Receptors
Knaus, U. G., Morris, S., Dong, H., Chernoff, J., & Bokoch, G. (1995) · Science · doi:10.1126/science.7618083 · Cited by 402 · see citing works
Combinatorial Control Required for the Specificity of Yeast MAPK Signaling
Madhani, H. D., & Fink, G. R. (1997) · Science · doi:10.1126/science.275.5304.1314 · Cited by 396 · see citing works
Signaling from the Small GTP-binding Proteins Rac1 and Cdc42 to the c-Jun N-terminal Kinase/Stress-activated Protein Kinase Pathway
Teramoto, H., Coso, O. A., Miyata, H., Igishi, T., Miki, T., & Gutkind, J. S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27225 · Cited by 343 · see citing works
A downstream target of RHO1 small GTP‐binding protein is PKC1, a homolog of protein kinase C, which leads to activation of the MAP kinase cascade in Saccharomyces cerevisiae.
Nonaka, H., Tanaka, K., Hirano, H., Fujiwara, T., Kohno, H., Umikawa, M., Mino, A., & Takai, Y. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00281.x · Cited by 341 · see citing works
Molecular Cloning and Characterization of a Novel p38 Mitogen-activated Protein Kinase
Wang, X. S., Diener, K., Manthey, C. L., Wang, S., Rosenzweig, B., Bray, J., Delaney, J., Cole, C. N., Chan-Hui, P.-Y., Mantlo, N. B., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.38.23668 · Cited by 331 · see citing works
ERK6, a mitogen-activated protein kinase involved in C2C12 myoblast differentiation.
Lechner, C., Zahalka, M. A., Giot, J.-F., Møller, N. P. H., & Ullrich, A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.9.4355 · Cited by 327 · see citing works
Activation of the Raf-1 kinase cascade by coumermycin-induced dimerization
Farrar, M. A., Alberola‐Ila, J., & Perlmutter, R. M. (1996) · Nature · doi:10.1038/383178a0 · Cited by 326 · see citing works
Activation of MEK‐1 and SEK‐1 by Tpl‐2 proto‐oncoprotein, a novel MAP kinase kinase kinase.
Salmerón, A., Ahmad, T. B., Carlile, G. W., Pappin, D., Narsimhan, R. P., & Ley, S. C. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00417.x · Cited by 300 · see citing works
Vertebrate evolution by interspecific hybridisation – are we polyploid?
Spring, J. (1997) · FEBS Letters · doi:10.1016/s0014-5793(96)01351-8 · Cited by 292 · 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
Actions of Rho Family Small G Proteins and p21-Activated Protein Kinases on Mitogen-Activated Protein Kinase Family Members
Frost, J. A., Xu, S., Hutchison, M. R., Marcus, S., & Cobb, M. H. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.7.3707 · Cited by 275 · see citing works
Inhibitory and activating functions for MAPK Kss1 in the S. cerevisiae filamentous- growth signalling pathway
Cook, J. G., Bardwell, L., & Thorner, J. W. (1997) · Nature · doi:10.1038/36355 · Cited by 258 · see citing works
A novel SAPK/JNK kinase, MKK7, stimulated by TNFα and cellular stresses
Moriguchi, T., Toyoshima, F., Masuyama, N., Hanafusa, H., Gotoh, Y., & Nishida, E. (1997) · The EMBO Journal · doi:10.1093/emboj/16.23.7045 · Cited by 250 · see citing works
Cloning of a Novel Mitogen-activated Protein Kinase Kinase Kinase, MEKK4, That Selectively Regulates the c-Jun Amino Terminal Kinase Pathway
Gerwins, P., Jonathan, L., & Johnson, G. L. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.13.8288 · Cited by 242 · see citing works
Oligomerization activates c-Raf-1 through a Ras-dependent mechanism
Luo, Z., Tzivion, G., Belshaw, P. J., Vavvas, D. G., Marshall, M. S., & Avruch, J. (1996) · Nature · doi:10.1038/383181a0 · Cited by 238 · see citing works
The Mixed Lineage Kinase SPRK Phosphorylates and Activates the Stress-activated Protein Kinase Activator, SEK-1
Rana, A., Gallo, K. A., Godowski, P. J., Hirai, S.-I., Ohno, S., Zon, L. I., Kyriakis, J. M., & Avruch, J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.32.19025 · Cited by 223 · see citing works
Protein Kinase C, but Not Tyrosine Kinases or Ras, Plays a Critical Role in Angiotensin II-induced Activation of Raf-1 Kinase and Extracellular Signal-regulated Protein Kinases in Cardiac Myocytes
Zou, Y., Komuro, I., Yamazaki, T., Aikawa, R., Kudoh, S., Shiojima, I., Hiroi, Y., Mizuno, T., & Yazaki, Y. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.52.33592 · Cited by 211 · see citing works
Isolation and characterization of two growth factor-stimulated protein kinases that phosphorylate the epidermal growth factor receptor at threonine 669
Northwood, I. C., Gonzalez, F. A., Wartmann, M., Raden, D. L., & Davis, R. J. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)98612-6 · Cited by 209 · see citing works
A new Rac target POSH is an SH3‐containing scaffold protein involved in the JNK and NF‐κB signalling pathways
Tapon, N., Nagata, K., Lamarche, N., & Hall, A. (1998) · The EMBO Journal · doi:10.1093/emboj/17.5.1395 · Cited by 207 · see citing works
Role for the Rho-family GTPase Cdc42 in yeast mating-pheromone signal pathway
Simon, M., VIRGILIO, C. D., Souza, B., Pringle, J. R., Abo, A., & Reed, S. I. (1995) · Nature · doi:10.1038/376702a0 · Cited by 204 · see citing works
A Proline-Rich Sequence Unique to MEK1 and MEK2 Is Required for Raf Binding and Regulates MEK Function
Catling, A. D., Schaeffer, H. J., Reuter, C. W., Reddy, G. R., & Weber, M. J. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.10.5214 · Cited by 197 · see citing works
A human homolog of the yeast Ssk2/Ssk22 MAP kinase kinase kinases, MTK1, mediates stress‐induced activation of the p38 and JNK pathways
Takekawa, M., Posas, F., & Saito, H. (1997) · The EMBO Journal · doi:10.1093/emboj/16.16.4973 · Cited by 193 · see citing works
Crystal structure of casein kinase‐1, a phosphate‐directed protein kinase.
Xu, R.-M., Carmel, G., Sweet, R. M., Kuret, J., & Cheng, X. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07082.x · Cited by 193 · see citing works
The coevolution of gene family trees
Fryxell, K. J. (1996) · Trends in Genetics · doi:10.1016/s0168-9525(96)80020-5 · Cited by 187 · see citing works
Pheromone Signalling in Saccharomyces cerevisiae Requires the Small GTP-Binding Protein Cdc42p and Its Activator CDC24
Zhao, Z.-S., Leung, T., Manser, E. J., & Lim, L. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.10.5246 · Cited by 187 · see citing works
The Mcs4 response regulator coordinately controls the stress-activated Wak1-Wis1-Sty1 MAP kinase pathway and fission yeast cell cycle.Preprint
Shieh, J., Wilkinson, M. G., Buck, V., Morgan, B. A., Makino, K., & Millar, J. B. A. (1997) · Genes & Development · doi:10.1101/gad.11.8.1008 · Cited by 179 · see citing works
MST/MLK2, a Member of the Mixed Lineage Kinase Family, Directly Phosphorylates and Activates SEK1, an Activator of c-Jun N-terminal Kinase/Stress-activated Protein Kinase
Hirai, S.-I., Katoh, M., Terada, M., Kyriakis, J. M., Zon, L. I., Rana, A., Avruch, J., & Ohno, S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.24.15167 · Cited by 178 · see citing works
The Small GTP-binding Protein Rho Activates c-Jun N-terminal Kinases/Stress-activated Protein Kinases in Human Kidney 293T Cells
Teramoto, H., Crespo, P., Coso, O. A., Igishi, T., Xu, N., & Gutkind, J. S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.42.25731 · Cited by 173 · see citing works
Extracellular Signal-Regulated Kinase 7 (ERK7), a Novel ERK with a C-Terminal Domain That Regulates Its Activity, Its Cellular Localization, and Cell Growth
Abe, M. K., Kuo, W.-L., Hershenson, M. B., & Rosner, M. R. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.2.1301 · Cited by 155 · see citing works
Activation of a human Ste20‐like kinase by oxidant stress defines a novel stress response pathway.
Pombo, C. M., Bonventre, J. V., Molnar, A., Kyriakis, J. M., & Force, T. L. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00831.x · Cited by 149 · see citing works
Two structures of the catalytic domain of phosphorylase kinase: an active protein kinase complexed with substrate analogue and product
Owen, D., Noble, M., Garman, E. F., Papageorigiou, A., & Johnson, L. (1995) · Structure · doi:10.1016/s0969-2126(01)00180-0 · Cited by 148 · see citing works
Delineation of the Cdc42/Rac-Binding Domain of p21-Activated Kinase
Thompson, G., Owen, D., Chalk, P. A., & Lowe, P. N. (1998) · Biochemistry · doi:10.1021/bi980140+ · Cited by 144 · see citing works
Dual Leucine Zipper-bearing Kinase (DLK) Activates p46SAPK and p38 but Not ERK2
Fan, G., Merritt, S. E., Kortenjann, M., Shaw, P. E., & Holzman, L. B. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.40.24788 · Cited by 140 · see citing works
Three-dimensional Structure of Mammalian Casein Kinase I: Molecular Basis for Phosphate Recognition
Longenecker, K. L., Roach, P. J., & Hurley, T. D. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0189 · Cited by 132 · see citing works
Activation of the JNK pathway by distantly related protein kinases, MEKK and MUK.
Hirai, S.-I., Izawa, M., Osada, S., Spyrou, G., & Ohno, S. (1996) · PubMed · Cited by 127 · see citing works
Characterization of the Mitogen-activated Protein Kinase Kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 Pathways Regulated by MEK Kinases 2 and 3
Deacon, K., & Blank, J. L. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.22.14489 · Cited by 111 · see citing works
Cloning and Characterization of a Human STE20-like Protein Kinase with Unusual Cofactor Requirements
Schinkmann, K. A., & Blenis, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.45.28695 · Cited by 109 · see citing works
Direct Activation of the Stress-activated Protein Kinase (SAPK) and Extracellular Signal-regulated Protein Kinase (ERK) Pathways by an Inducible Mitogen-activated Protein Kinase/ERK Kinase Kinase 3 (MEKK) Derivative
Ellinger-Ziegelbauer, H. C., Brown, K., Kelly, K., & Siebenlist, U. K. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.5.2668 · Cited by 102 · see citing works
Activation of Stress-activated Protein Kinases/c-Jun N-terminal Protein Kinases (SAPKs/JNKs) by a Novel Mitogen-activated Protein Kinase Kinase (MKK7)
Yao, Z., Diener, K., Wang, X. S., Zukowski, M. M., Matsumoto, G., Zhou, G., Mo, R., Sasaki, T., Nishina, H., Hui, C.-C., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.51.32378 · Cited by 96 · see citing works
Escaping from the Felsenstein Zone by Detecting Long Branches in Phylogenetic Data
Lyons‐Weiler, J., & Hoelzer, G. A. (1997) · Molecular Phylogenetics and Evolution · doi:10.1006/mpev.1997.0450 · Cited by 91 · see citing works
Molecular Cloning and Functional Expression of a cDNA Encoding a New Member of Mixed Lineage Protein Kinase from Human Brain
Sakuma, H., Ikeda, A., Oka, S., Kozutsumi, Y., Zanetta, J., & Kawasaki, T. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.45.28622 · Cited by 86 · see citing works
Complementation of byrl in fission yeast by mammalian MAP kinase kinase requires coexpression of Raf kinase
Hughes, D. A., Ashworth, A., & Marshall, C. J. (1993) · Nature · doi:10.1038/364349a0 · Cited by 77 · see citing works
Protein Kinase Byr2 Is a Target of Ras1 in the Fission Yeast Schizosaccharomyces pombe
Masuda, T., Kariya, K., Shinkai, M., Okada, T., & Kataoka, T. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.5.1979 · Cited by 73 · see citing works
The MEK1 Proline-rich Insert Is Required for Efficient Activation of the Mitogen-activated Protein Kinases ERK1 and ERK2 in Mammalian Cells
Dang, A., Frost, J. A., & Cobb, M. H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.31.19909 · Cited by 69 · see citing works
Cloning and characterization of p97MAPK, a novel human homolog of rat ERK-3.
Zhu, A. X., Zhao, Y., Moller, D. E., & Flier, J. S. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.12.8202 · Cited by 66 · see citing works
Interaction of Rac1 with GTPase-activating Proteins and Putative Effectors
Zhang, B., Chernoff, J., & Zheng, Y. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.15.8776 · Cited by 63 · see citing works
The Dictyostelium dual-specificity kinase splA is essential for spore differentiation
Nuckolls, G. H., Osherov, N., Loomis, W. F., & Spudich, J. A. (1996) · Development · doi:10.1242/dev.122.10.3295 · Cited by 44 · see citing works
Control of MAP kinase signaling specificity or how not to go HOG wild: Figure 1.Preprint
Sprague, G. F. (1998) · Genes & Development · doi:10.1101/gad.12.18.2817 · Cited by 42 · see citing works
YSK1, a novel mammalian protein kinase structurally related to Ste20 and SPS1, but is not involved in the known MAPK pathways
Osada, S., Izawa, M., Saito, R., Mizuno, K., Suzuki, A., Hirai, S.-I., & Ohno, S. (1997) · Oncogene · doi:10.1038/sj.onc.1201043 · Cited by 35 · see citing works
Protein-protein interactions in the yeastPKC1 pathway: Pkc1p interacts with a component of the MAP kinase cascade
Paravicini, G., & Friedli, L. (1996) · Molecular and General Genetics MGG · doi:10.1007/bf02174117 · Cited by 30 · see citing works
The evolution of haematopoietic cytokine /receptor complexes
Shields, D. C., Harmon, D. L., Nunez, F., & Whitehead, A. S. (1995) · Cytokine · doi:10.1006/cyto.1995.0080 · Cited by 22 · see citing works
Self-citation
Tyrosine Phosphorylation of Extracellular Signal‐Regulated Protein Kinase 4 in Response to Growth Factors
Peng, X., Angelastro, J. M., & Greene, L. A. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66031191.x · Cited by 22 · see citing works
Phylogenetic analysis and comparative genomics
LAKE, J. (1998) · Trends in biotechnology · doi:10.1016/s0167-7799(98)00132-2 · Cited by 18 · see citing works
Dominant Mutations of Drosophila MAP Kinase Kinase and Their Activities in Drosophila and Yeast MAP Kinase Cascades
Lim, Y., Tsuda, L., Inoue, Y. H., Irie, K., Adachi‐Yamada, T., Hata, M., Nishi, Y., Matsumoto, K., & Nishida, Y. (1997) · Genetics · doi:10.1093/genetics/146.1.263 · Cited by 16 · see citing works

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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
Mitogen-activated protein kinases in apoptosis regulation
Wada, T., & Penninger, J. M. (2004) · Oncogene · doi:10.1038/sj.onc.1207556 · Cited by 1,432 · see citing works
Functional Divergence of Duplicated Genes Formed by Polyploidy during Arabidopsis Evolution[W]
Blanc, G., & Wolfe, K. H. (2004) · The Plant Cell · doi:10.1105/tpc.021410 · Cited by 1,068 · see citing works
MAP Kinases
Chen, Z., Gibson, T. B., Robinson, F. L., Silvestro, L., Pearson, G. W., Xu, B.-E., Wright, A., Vanderbilt, C. A., & Cobb, M. H. (2001) · Chemical Reviews · doi:10.1021/cr000241p · Cited by 789 · see citing works
The Interleukin-1 Receptor/Toll-Like Receptor Superfamily: Signal Transduction During Inflammation and Host Defense
Dunne, A., & O'Neill, L. A. J. (2003) · Science s STKE · doi:10.1126/stke.2003.171.re3 · Cited by 712 · see citing works
Self-citation
MAPK cascades in plant defense signaling
Zhang, S., & Klessig, D. F. (2001) · Trends in Plant Science · doi:10.1016/s1360-1385(01)02103-3 · Cited by 773 · see citing works
Targeting dual-specificity phosphatases: Manipulating MAP kinase signalling and immune responses
Jeffrey, K. L., Camps, M., Rommel, C., & Mackay, C. R. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2289 · Cited by 533 · see citing works
MAP kinase pathways
Qi, M., & Elion, E. A. (2005) · Journal of Cell Science · doi:10.1242/jcs.02470 · Cited by 524 · see citing works
Cell Death Mediated by MAPK Is Associated with Hydrogen Peroxide Production in Arabidopsis
Ren, D., Yang, H., & Zhang, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109495200 · Cited by 459 · see citing works
Distinct Roles for JNK1 and JNK2 in Regulating JNK Activity and c-Jun-Dependent Cell Proliferation
Sabapathy, K., Hochedlinger, K., Nam, S. Y., Bauer, A., Karin, M., & Wagner, E. F. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.08.028 · Cited by 397 · see citing works
Intrinsic disorder in scaffold proteins: Getting more from less
Cortese, M. S., Uversky, V. N., & Dunker, A. K. (2008) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2008.05.007 · Cited by 292 · see citing works
Yeast go the whole HOG for the hyperosmotic response
O’Rourke, S. M., Herskowitz, I., & O’Shea, E. K. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(02)02723-3 · Cited by 275 · see citing works
The control of cell motility and epithelial morphogenesis by Jun kinases
Xia, Y., & Karin, M. (2004) · Trends in Cell Biology · doi:10.1016/j.tcb.2003.12.005 · Cited by 242 · see citing works
Persistence of vibrios in marine bivalves: the role of interactions with haemolymph components
Pruzzo, C., Gallo, G., & Canesi, L. (2005) · Environmental Microbiology · doi:10.1111/j.1462-2920.2005.00792.x · Cited by 230 · see citing works
The Ste5p scaffold
Elion, E. A. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.22.3967 · Cited by 226 · see citing works
Hog1: 20 years of discovery and impact
Brewster, J. L., & Gustin, M. C. (2014) · Science Signaling · doi:10.1126/scisignal.2005458 · Cited by 197 · see citing works
p38 MAPK signalling cascades: ancient roles and new functions
Martı́n-Blanco, E. (2000) · BioEssays · doi:10.1002/1521-1878(200007)22:7 · Cited by 189 · see citing works
Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove
Garai, Á., Zeke, A., Gógl, G., Törő, I., Fördős, F., Blankenburg, H., Bárkai, T., Varga, J., Alexa, A., Emig, D., et al. (2012) · Science Signaling · doi:10.1126/scisignal.2003004 · Cited by 177 · see citing works
Integration of Caenorhabditis elegans MAPK pathways mediating immunity and stress resistance by MEK-1 MAPK kinase and VHP-1 MAPK phosphatase
Kim, D. H., Liberati, N. T., Mizuno, T., Inoue, H., Hisamoto, N., Matsumoto, K., & Ausubel, F. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403546101 · Cited by 184 · see citing works
A Conserved Docking Site in MEKs Mediates High-affinity Binding to MAP Kinases and Cooperates with a Scaffold Protein to Enhance Signal Transmission
Bardwell, A. J., Flatauer, L. J., Matsukuma, K. E., Thorner, J. W., & Bardwell, L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010271200 · Cited by 177 · see citing works
Activation of Salicylic Acid–Induced Protein Kinase, a Mitogen-Activated Protein Kinase, Induces Multiple Defense Responses in Tobacco
Zhang, S., & Liu, Y. (2001) · The Plant Cell · doi:10.1105/tpc.010044 · Cited by 172 · see citing works
Evolutionary perspectives on innate immunity from the study of Caenorhabditis elegans
Kim, D. H., & Ausubel, F. M. (2004) · Current Opinion in Immunology · doi:10.1016/j.coi.2004.11.007 · Cited by 145 · see citing works
Identification of new members of the MAPK gene family in plants shows diverse conserved domains and novel activation loop variants
Mohanta, T. K., Arora, P. K., Mohanta, N., Parida, P. K., & Bae, H. (2015) · BMC Genomics · doi:10.1186/s12864-015-1244-7 · Cited by 139 · see citing works
Taxol-induced mitochondrial stress in melanoma cells is mediated by activation of c-Jun N-terminal kinase (JNK) and p38 pathways via uncoupling protein 2
Selimović, D., Hassan, M., Haïkel, Y., & Hengge, U. R. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.10.015 · Cited by 134 · see citing works
Anti-inflammatory Therapy of Dry Eye
Pflugfelder, S. C. (2003) · The Ocular Surface · doi:10.1016/s1542-0124(12)70005-8 · Cited by 114 · see citing works
Fusarium Phytotoxin Trichothecenes Have an Elicitor-Like Activity in Arabidopsis thaliana, but the Activity Differed Significantly Among Their Molecular Species
Nishiuchi, T., Masuda, D., Nakashita, H., Ichimura, K., Shinozaki, K., Yoshida, S., Kimura, M., Yamaguchi, I., & Yamaguchi, K. (2006) · Molecular Plant-Microbe Interactions · doi:10.1094/mpmi-19-0512 · Cited by 104 · see citing works
Gene Dosage Balance in Cellular Pathways
Veitia, R. A. (2004) · Genetics · doi:10.1534/genetics.104.029785 · Cited by 98 · see citing works
Signaling pathways involved in the physiological response of mussel hemocytes to bacterial challenge: the role of stress-activated p38 MAP kinases
Canesi, L., Betti, M., Ciacci, C., Scarpato, A., Citterio, B., Pruzzo, C., & Gallo, G. (2002) · Developmental & Comparative Immunology · doi:10.1016/s0145-305x(01)00078-7 · Cited by 93 · see citing works
The small GTPase Rac and the p21‐activated kinase Cla4 in Claviceps purpurea: interaction and impact on polarity, development and pathogenicity
Rolke, Y., & Tudzynski, P. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06159.x · Cited by 90 · see citing works
Spatial and temporal signal processing and decision making by MAPK pathways
Atay, O., & Skotheim, J. M. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201609124 · Cited by 89 · see citing works
Antagonistic control of cell fates by JNK and p38-MAPK signaling
Wada, T., Stępniak-Konieczna, E., Hui, L., Leibbrandt, A., Katada, T., Nishina, H., Wagner, E. F., & Penninger, J. M. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402222 · Cited by 79 · see citing works
Methyl jasmonate decreases membrane fluidity and induces apoptosis through tumor necrosis factor receptor 1 in breast cancer cells
Yeruva, L., Elegbede, J. A., & Carper, S. W. (2008) · Anti-Cancer Drugs · doi:10.1097/cad.0b013e32830b5894 · Cited by 73 · see citing works
Evolutionary History of the Vertebrate Mitogen Activated Protein Kinases Family
Li, M., Liu, J., & Zhang, C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026999 · Cited by 72 · see citing works
The mitogen-activated protein kinome from Anopheles gambiae: identification, phylogeny and functional characterization of the ERK, JNK and p38 MAP kinases
Horton, A. A., Wang, B., Camp, L. E., Price, M. S., Arshi, A., Nagy, M., Nadler, S. A., Faeder, J. R., & Luckhart, S. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-574 · Cited by 64 · see citing works
Cadmium-Induced Germline Apoptosis in Caenorhabditis elegans: The Roles of HUS1, p53, and MAPK Signaling Pathways
Wang, S., Tang, M., Pei, B., Xiao, X., Wang, J., Hang, H., & Wu, L. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfm220 · Cited by 62 · see citing works
Oxidative Stress ActivatesFUS1andRLM1Transcription in the YeastSaccharomyces cerevisiaein an Oxidant-dependent Manner
Staleva, L., Hall, A., & Orlow, S. J. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-02-0142 · Cited by 56 · see citing works
Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans*
Andrusiak, M., & Jin, Y.-S. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.711101 · Cited by 55 · see citing works
Effects of tumour necrosis factor α (TNFα) on Mytilus haemocytes: role of stress‐activated mitogen‐activated protein kinases (MAPKs)
Betti, M., Ciacci, C., Lorusso, L. C., Canonico, B., Falcioni, T., Gallo, G., & Canesi, L. (2006) · Biology of the Cell · doi:10.1042/bc20050049 · Cited by 55 · see citing works
Interactions between Mytilus haemocytes and different strains of Escherichia coli and Vibrio cholerae O1 El Tor: role of kinase-mediated signalling
Canesi, L., Betti, M., Ciacci, C., Lorusso, L. C., Gallo, G., & Pruzzo, C. (2005) · Cellular Microbiology · doi:10.1111/j.1462-5822.2005.00499.x · Cited by 54 · see citing works
Promising effects of gingerol against toxins: A review article
Yahyazadeh, R., Rahimi, V. B., Yahyazadeh, A., Mohajeri, S. A., & Askari, V. R. (2021) · BioFactors · doi:10.1002/biof.1779 · Cited by 52 · see citing works
Analysis of mitogen-activated protein kinase activation and interactions with regulators and substrates
BARDWELL, L., & SHAH, K. (2006) · Methods · doi:10.1016/j.ymeth.2006.06.008 · Cited by 46 · see citing works
Molecular characterisation of MEK1/2- and MKK3/6-like mitogen-activated protein kinase kinases (MAPKK) from the fox tapeworm Echinococcus multilocularis
Gelmedin, V., Spiliotis, M., & Brehm, K. (2009) · International Journal for Parasitology · doi:10.1016/j.ijpara.2009.10.009 · Cited by 48 · see citing works
Regulation of Cell-to-Cell Communication and Cell Wall Integrity by a Network of MAP Kinase Pathways and Transcription Factors in Neurospora crassa
Fischer, M. S., Wu, V. W., Lee, J. E., O’Malley, R. C., & Glass, N. L. (2018) · Genetics · doi:10.1534/genetics.118.300904 · Cited by 46 · see citing works
Genomic analysis of MAP kinase cascades inArabidopsis defense responses
Cvetkovska, M., Rampitsch, C., Bykova, N. V., & Xing, T. (2005) · Plant Molecular Biology Reporter · doi:10.1007/bf02788882 · Cited by 46 · see citing works
Properties and Regulation of a Transiently Assembled ERK2·Ets-1 Signaling Complex
Callaway, K., Rainey, M. A., Riggs, A., Abramczyk, O., & Dalby, K. N. (2006) · Biochemistry · doi:10.1021/bi0610451 · Cited by 45 · see citing works
Copper-induced germline apoptosis in Caenorhabditis elegans: The independent roles of DNA damage response signaling and the dependent roles of MAPK cascades
Wang, S., Wu, L., Wang, Y., Luo, X., & Lu, Y. (2009) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2009.03.012 · Cited by 45 · see citing works
The Interleukin-1 Receptor/Toll-like Receptor Superfamily: Signal Transduction During Inflammation and Host Defense
O'Neill, L. A. J. (2000) · Science s STKE · doi:10.1126/stke.442000re1 · Cited by 43 · see citing works
Self-citation
Mitogen-activated protein kinase (MAPK)-docking sites in MAPK kinases function as tethers that are crucial for MAPK regulation in vivo
Grewal, S., Molina, D. M., & Bardwell, L. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2005.04.001 · Cited by 41 · see citing works
Schistosoma mansoni excretory–secretory products stimulate a p38 signalling pathway in Biomphalaria glabrata embryonic cells
Humphries, J. E., & Yoshino, T. P. (2005) · International Journal for Parasitology · doi:10.1016/j.ijpara.2005.08.009 · Cited by 39 · see citing works
Conservation of the positions of metazoan introns from sponges to humans
Müller, W. E. G., Böhm, M., Grebenjuk, V. A., Skorokhod, A., Müller, I. M., & Gamulin, V. (2002) · Gene · doi:10.1016/s0378-1119(02)00690-x · Cited by 38 · see citing works
Structural Mechanism for the Specific Assembly and Activation of the Extracellular Signal Regulated Kinase 5 (ERK5) Module
Glatz, G., Gógl, G., Alexa, A., & Reményi, A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.452235 · Cited by 36 · see citing works
Characterization of an ERK-binding Domain in Microphthalmia-associated Transcription Factor and Differential Inhibition of ERK2-mediated Substrate Phosphorylation
Molina, D. M., Grewal, S., & Bardwell, L. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m510590200 · Cited by 36 · see citing works
Functional Convergence of Invertebrate and Vertebrate Cytokine-Like Molecules Based on a Similar Lectin-Like Activity
Beschin, A., Bilej, M., Magez, S., Lucas, R., & BAETSELIER, P. D. (2003) · Progress in molecular and subcellular biology · doi:10.1007/978-3-642-18670-7_6 · Cited by 35 · see citing works
The genome-wide identification of mitogen-activated protein kinase kinase (MKK) genes in Yesso scallop Patinopecten yessoensis and their expression responses to bacteria challenges
Zou, J., Wang, R., Li, R., Kong, Y., Wang, J., Ning, X., Zhang, L., Wang, S., Hu, X., & Bao, Z. (2015) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2015.06.006 · Cited by 34 · see citing works
When expressed in yeast, mammalian mitogen-activated protein kinases lose proper regulation and become spontaneously phosphorylated
Levin‐Salomon, V., Maayan, I., Avrahami‐Moyal, L., Marbach, I., Livnah, O., & Engelberg, D. (2008) · Biochemical Journal · doi:10.1042/bj20081335 · Cited by 33 · see citing works
Microcystin‐LR induces cytotoxicity and affects carp immune cells by impairment of their phagocytosis and the organization of the cytoskeleton
Rymuszka, A. (2012) · Journal of Applied Toxicology · doi:10.1002/jat.2791 · Cited by 32 · see citing works
c-Jun N-Terminal Kinase 1 Phosphorylates Myt1 To Prevent UVA-Induced Skin Cancer
Choi, H. S., Bode, A. M., Shim, J., Lee, S., & Dong, Z. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01508-08 · Cited by 31 · see citing works
SREBP‐1: Gene Regulatory Key to Syndrome X?
Müller‐Wieland, D., & Kotzka, J. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04259.x · Cited by 31 · see citing works
ERK5 Pathway Regulates Transcription Factors Important for Monocytic Differentiation of Human Myeloid Leukemia Cells
Wang, X., Pesakhov, S., Harrison, J. S., Danilenko, M., & Studzinski, G. P. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24513 · Cited by 29 · see citing works
HvJNK, a Hydra member of the c-Jun NH2-terminal kinase gene family, is expressed during nematocyte differentiation
Philipp, I., Holstein, T. W., & Hobmayer, B. (2004) · Gene Expression Patterns · doi:10.1016/j.modgep.2004.09.007 · Cited by 29 · see citing works
NK007 helps in mitigating paclitaxel resistance through p38MAPK activation and HK2 degradation in ovarian cancer
Li, Z., Tang, X., Luo, Y., Chen, B., Zhou, C., Wu, X., Tang, Z., Qi, X., Cao, G., Hao, J., et al. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28278 · Cited by 28 · see citing works
Activation of JNK and p38 in MCF-7 Cells and the In Vitro Anticancer Activity of Alnus hirsuta Extract
Ryu, M., Sung, C. K., Im, Y. J., & Chun, C. (2020) · Molecules · doi:10.3390/molecules25051073 · Cited by 28 · see citing works
Arsenite-Induced Germline Apoptosis through a MAPK-Dependent, p53-independent Pathway in Caenorhabditis elegans
Pei, B., Wang, S., Guo, X., Wang, J., Yang, G., Hang, H., & Wu, L. (2008) · Chemical Research in Toxicology · doi:10.1021/tx800074e · Cited by 25 · see citing works
Expression and sequence analysis of the Blumeria graminis mitogen-activated protein kinase genes, mpk 1 and mpk 2
Zhang, Z., & Gurr, S. J. (2001) · Gene · doi:10.1016/s0378-1119(01)00381-x · Cited by 25 · see citing works
De novo characterization of the liver transcriptome of javelin goby Synechogobius hasta and analysis of its transcriptomic profile following waterborne copper exposure
Chen, Q.-L., Luo, Z., Huang, C., Pan, Y., & Wu, K. (2015) · Fish Physiology and Biochemistry · doi:10.1007/s10695-015-0190-2 · Cited by 23 · see citing works
Normalized cDNA libraries from a porcine model of orthopedic implant-associated infection
Rink, A., Santschi, E. M., & Beattie, C. W. (2002) · Mammalian Genome · doi:10.1007/s00335-001-2120-0 · Cited by 23 · see citing works
Droplet-based screening of phosphate transfer catalysis reveals how epistasis shapes MAP kinase interactions with substrates
Scheele, R. A., Lindenburg, L. H., Petek, M., Schober, M., Dalby, K. N., & Hollfelder, F. (2022) · Nature Communications · doi:10.1038/s41467-022-28396-4 · Cited by 20 · see citing works
p38α MAP Kinase Dimers with Swapped Activation Segments and a Novel Catalytic Loop Conformation
Rothweiler, U., Åberg, E., Johnson, K. A., Hansen, T. E., Jørgensen, J. B., & Engh, R. A. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.06.013 · Cited by 20 · see citing works
Nickel-induced apoptosis and relevant signal transduction pathways in Caenorhabditis elegans
Cai, K., Chong, R., & Yu, Z. (2010) · Toxicology and Industrial Health · doi:10.1177/0748233710364962 · Cited by 20 · see citing works
The Protein Kinase ERK3 Is Encoded by a Single Functional Gene: Genomic Analysis of the ERK3 Gene Family
Turgeon, B., Lang, B. F., & Meloche, S. (2002) · Genomics · doi:10.1006/geno.2002.7013 · Cited by 20 · see citing works
A method to predict residues conferring functional differences between related proteins: Application to MAP kinase pathways
Caffrey, D. R., Shields, D. C., & O'Neill, L. A. J. (2000) · Protein Science · doi:10.1110/ps.9.4.655 · Cited by 20 · see citing works
Self-citation
Identification and characterization of alcohol-soluble components from wheat germ-apple fermented by Lactobacillus sp. capable of preventing ulcerative colitis of dextran sodium sulfate-induced mice
He, D., Wang, Y., Lin, J., Xing, Y.-F., Zeng, W., Zhu, W., Su, N., Zhang, C., Lu, Y., & Xing, X. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.103642 · Cited by 19 · see citing works
MAP Kinase Mediated Activation of RSK1 and MK2 Substrate Kinases
Sok, P., Gógl, G., Kumar, G. S., Alexa, A., Singh, N., Kirsch, K., Sebő, A., Drahos, L., Gáspári, Z., Peti, W., et al. (2020) · Structure · doi:10.1016/j.str.2020.06.007 · Cited by 20 · see citing works
Involvement of intracellular signaling cascades in inflammatory responses in human intestinal epithelial cells following Vibrio cholerae infection
Bandyopadhaya, A., Das, D., & Chaudhuri, K. (2008) · Molecular Immunology · doi:10.1016/j.molimm.2008.11.003 · Cited by 19 · see citing works
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Palacios, L., Dickinson, R. J., Sacristán-Reviriego, A., Didmon, M. P., Marín, M. J., Martı́n, H., Keyse, S. M., & Molina, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.286948 · Cited by 19 · see citing works
Genome-Wide Analyses of Metal Responsive Genes in Caenorhabditis elegans
Caito, S. W., Fretham, S. J. B., Martinez‐Finley, E. J., Chakraborty, S., Ávila, D. S., Chen, P., & Aschner, M. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00052 · Cited by 18 · see citing works
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Saha, P., Katarkar, A., Das, B., Bhattacharyya, A., & Chaudhuri, K. (2016) · Pharmaceutical Biology · doi:10.3109/13880209.2015.1110598 · Cited by 18 · see citing works
Signaling pathways involved in metal-based nanomaterial toxicity towards aquatic organisms
Châtel, A., & Mouneyrac, C. (2017) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2017.03.014 · Cited by 18 · see citing works
TheSalmonellaTyphimurium effector SteC inhibits Cdc42-mediated signaling through binding to the exchange factor Cdc24 inSaccharomyces cerevisiae
Fernández-Piñar, P., Alemán, A., Sondek, J., Dohlman, H. G., Molina, M., & Martı́n, H. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e12-03-0243 · Cited by 18 · see citing works
Sequence analysis of multidomain proteins: Past perspectives and future directions
Copley, R. R., Ponting, C. P., Schultz, J., & Peer Bork, B. (2002) · Advances in protein chemistry · doi:10.1016/s0065-3233(02)61002-2 · Cited by 17 · see citing works
Microfluidics in Single Cell Analysis
Beck, C., & Goksr, M. (2012) · InTech eBooks · doi:10.5772/37154 · Cited by 17 · see citing works
Unfolding the Endoplasmic Reticulum of a Social Amoeba: Dictyostelium discoideum as a New Model for the Study of Endoplasmic Reticulum Stress
Domínguez‐Martín, E., Hernández-Elvira, M., Vincent, O., Coria, R., & Escalante, R. (2018) · Cells · doi:10.3390/cells7060056 · Cited by 16 · see citing works
Epitope-Guided Engineering of Monobody Binders for in Vivo Inhibition of Erk-2 Signaling
Mann, J. K., Wood, J. F., Stephan, A. F., Tzanakakis, E. S., Ferkey, D. M., & Park, S. (2012) · ACS Chemical Biology · doi:10.1021/cb300579e · Cited by 16 · see citing works
The evolution of signaling complexity suggests a mechanism for reducing the genomic search space in human association studies
Irizarry, K. J. L., Merriman, B., Bahamonde, M. E., Wong, M., & Licinio, J. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001576 · Cited by 16 · see citing works
Variation and evolution of biomolecular systems: Searching for functional relevance
Huynen, M. A., Gabaldón, T., & Snel, ‎. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.02.004 · Cited by 15 · see citing works
The Caenorhabditis elegans Model of Legionella Infection
Brassinga, A. K. C., & Sifri, C. D. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-161-5_27 · Cited by 14 · see citing works
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Li, C., Kong, F., Sun, P., Bi, G., Li, N., Mao, Y., & Sun, M. (2018) · Journal of Applied Phycology · doi:10.1007/s10811-018-1412-7 · Cited by 13 · see citing works
Host Signal Transduction and Protein Kinases Implicated in Legionella Infection
Hempstead, A. D., & Isberg, R. R. (2013) · Current topics in microbiology and immunology · doi:10.1007/82_2013_342 · Cited by 13 · see citing works
Identification, structure, and phylogenetic relationships of a mitogen-activated protein kinase homologue from the parasitic protist Entamoeba histolytica
Ray, D., Dutta, S., Banerjee, S., Banerjee, R., & Raha, S. (2005) · Gene · doi:10.1016/j.gene.2004.10.026 · Cited by 13 · see citing works
Genome-wide analysis of the hard clam mitogen-activated protein kinase kinase gene family and their transcriptional profiles under abiotic stress
Hu, Z., Song, H., Feng, J., Zhou, C., Yang, M., Pu, S., Yu, Z., Li, Y., Guo, Y., Li, H., et al. (2022) · Marine Environmental Research · doi:10.1016/j.marenvres.2022.105606 · Cited by 12 · see citing works
Oxygen- and temperature-dependent expression of survival protein kinases in crucian carp (Carassius carassius) heart and brain
Nilsson, G., Vaage, J., & Stensløkken, K. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00094.2014 · Cited by 12 · see citing works
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Mohanta, T. K., Mohanta, N., Parida, P. K., & Bae, H. (2015) · Biological Procedures Online · doi:10.1186/s12575-015-0025-7 · Cited by 12 · see citing works
Rewiring MAP kinases in Saccharomyces cerevisiae to regulate novel targets through ubiquitination
Groves, B., Khakhar, A., Nadel, C. M., Gardner, R. G., & Seelig, G. (2016) · eLife · doi:10.7554/elife.15200 · Cited by 11 · see citing works
The potential for signal integration and processing in interacting MAP kinase cascades
Schwacke, J. H., & Voit, E. O. (2007) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2006.12.035 · Cited by 12 · see citing works
Evolutionary analysis of p38 stress-activated kinases in unicellular relatives of animals suggests an ancestral function in osmotic stress
Shabardina, V., Charria, P. R., Saborido, G. B., Díaz‐Mora, E., Cuenda, A., Ruiz‐Trillo, I., & Sanz‐Ezquerro, J. J. (2023) · Open Biology · doi:10.1098/rsob.220314 · Cited by 10 · see citing works
Upregulation of hippocampal extracellular signal-regulated kinase (ERK)–2 induces antidepressant-like behavior in the rat forced swim test.
Iñiguez, S. D., Parise, L. F., Lobo, M. K., Flores‐Ramirez, F. J., Garcia-Carachure, I., Warren, B. L., & Robison, A. J. (2019) · Behavioral Neuroscience · doi:10.1037/bne0000303 · Cited by 9 · see citing works
Gene divergence and pathway duplication in the metabolic network of yeast and digital organisms
Gerlee, P., Lundh, T., Zhang, B., & Anderson, A. R. A. (2009) · Journal of The Royal Society Interface · doi:10.1098/rsif.2008.0514 · Cited by 8 · see citing works
The necessity of investigating a freshwater-marine continuum using a mesocosm approach in nanosafety: The case study of TiO2 MNM-based photocatalytic cement
Châtel, A., Auffan, M., Ettajani, H., Brousset, L., Métais, I., Chaurand, P., Mouloud, M., Clavaguera, S., Gandolfo, Y., Bruneau, M., et al. (2020) · NanoImpact · doi:10.1016/j.impact.2020.100254 · Cited by 8 · see citing works
Isolation of intrinsically active mutants of MAP kinases via genetic screens in yeast
Engelberg, D., & Livnah, O. (2006) · Methods · doi:10.1016/j.ymeth.2006.06.014 · Cited by 8 · see citing works
From growth to stress: RAF-like kinases as integrators of hormonal signals in plants
Park, H. L., & Yoon, G. M. (2025) · Journal of Experimental Botany · doi:10.1093/jxb/eraf086 · Cited by 7 · see citing works

Analysis of the MAPK pathways, in silico and in vitro
Caffrey, D. R. (2002) · Arrow@dit (Dublin Institute of Technology)
Self-citation
Reconstructing the deep phylogeny of the MAPK signaling network: functional specialization via multi-tier coevolutionary expansionPreprint
Huang, E. J., Parksong, J., Peterson, A. F., Torres, F., Regot, S., & Bever, G. S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.01.616093
Refined Phylogenetic Ortholog Inference Reveals Coevolutionary Expansion of the MAPK Signaling Network Through Finetuning of Pathway Specificity
Huang, E. J., Parksong, J., Peterson, A. F., Torres, F., Regot, S., & Bever, G. S. (2025) · Journal of Molecular Evolution · doi:10.1007/s00239-025-10254-8 · Cited by 3 · see citing works
Mitogen and stress response pathways: MAP kinase cascades and phosphatase regulation in mammals and yeast
Waskiewicz, A. J., & Cooper, J. A. (1995) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(95)80063-8 · Cited by 575 · see citing works
Principles of MAP Kinase Signaling Specificity inSaccharomyces cerevisiae
Schwartz, M. A., & Madhani, H. D. (2004) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.073003.112634 · Cited by 239 · see citing works

Authors: Caffrey, D. R., O'Neill, L. A. J., & Shields, D. C.
Affiliations: Royal College of Surgeons in Ireland (IE)
Trinity College Dublin (IE)
ORCID: O'Neill, Luke A.J.
Shields, Denis C.
Venue: Journal of Molecular Evolution
Publisher: Springer Science and Business Media LLC
Published: 1999-11
Volume: 49
Issue: 5
Pages: 567-582
ISSN: 0022-2844 (ISSN-L)
DOI: 10.1007/pl00006578
OpenAlex: W2127534631
Cited by: 124
References: 106
Citations by year: 2026: 1 · 2025: 3 · 2024: 1 · 2023: 7 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 3 · 2013: 4 · 2012: 7
FWCI: 2.30
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Journal of Molecular Evolution (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords: MAPK signaling, gene duplication, JNK signaling, p38 pathway, pheromone signaling, pathway crosstalk, substrate specificity, yeast, Caenorhabditis elegans, mammalian evolution
MeSH terms: Animals, Mammals, Models, Genetic, Osmosis, Pheromones, Phylogeny, Saccharomyces cerevisiae, Spores, Fungal, Substrate Specificity, Signal Transduction, Caenorhabditis elegans, Protein Serine-Threonine Kinases, Oxidative Stress, Evolution, Molecular, Gene Duplication, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase Kinases, MAP Kinase Kinase Kinases, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins

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The Evolution of the MAP Kinase Pathways: Coduplication of Interacting Proteins Leads to New Signaling Cascades

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