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Mitogen-Activated Protein Kinases: Specific Messages from Ubiquitous Messengers
Open accessAbstract
Signal transduction networks allow cells to perceive changes in the extracellular environment and to mount an appropriate response. Mitogen-activated protein kinase (MAPK) cascades are among the most thoroughly studied of signal transduction systems and have been shown to participate in a diverse array of cellular programs, including cell differentiation, cell movement, cell division, and cell death. A key question in studies of this cascade is, how does a ubiquitously activated regulatory enzume generate a specific and biologically appropriate cellular response? In this review we describe recent findings that provide insight into ways that the regulation, structure, and localization of MAPKs and the participation of adapters and scaffolds can help determine biological outcomes. MAPK cascades are evolutionarily conserved in all eucaryotes and play a key role in the regulation of gene expression as well as cytoplasmic activities. They typically are organized in a three-kinase architecture consisting of a MAPK, a MAPK activator (MEK, MKK, or MAPK kinase), and a MEK activator (MEK kinase [MEKK] or MAPK kinase kinase). Transmission of signals is achieved by sequential phosphorylation and activation of the components specific to a respective cascade. In the yeast Saccharomyces cerevisiae, five MAPK modules have been described; they regulate mating, filamentation, high-osmolarity responses, cell wall remodeling, and sporulation (Fig. (Fig.1A)1A) (reviewed in references 56 and 77). In mammalian systems five distinguishable MAPK modules have been identified so far (Fig. (Fig.1B).1B). These include the extracellular signal-regulated kinase 1 and 2 (ERK1/2) cascade, which preferentially regulates cell growth and differentiation, as well as the c-Jun N-terminal kinase (JNK) and p38 MAPK cascades, which function mainly in stress responses like inflammation and apoptosis (reviewed in references 57, 74, and 103). Moreover, MAPK pathways control several developmental programs, such as morphogenesis and spatial patterning in Dictyostelium amoebae (17, 45), eye development in Drosophila melanogaster (124), vulva induction in Caenorhabditis elegans (113), and T-cell development in mammals (31). FIG. 1 Schematic overview of MAPK modules. (A) In S. cerevisiae, five MAPK modules regulate mating, filamentation, high-osmolarity responses, cell wall remodeling, and sporulation. (B) Mammalian MAPK modules regulate cell growth, differentiation, stress responses, ... Individual MAPK modules generally can signal independently from each other, and this specificity is manifested in distinct physiologic responses. This is most obvious when studying MAPK signaling in S. cerevisiae. Here a particular extracellular event characteristically activates a specific MAPK module and initiates a unique cellular program (reviewed in references 56 and 77). For example, stimulation of cells with pheromone leads to the activation of the pheromone response pathway (STE11, STE7, and FUS3) (Fig. (Fig.2),2), which ultimately results in cell cycle arrest and the induction of mating-specific genes. However, related MAPKs whose modules share some components with the pheromone response pathway are not affected by pheromone stimulation but are activated only in response to the appropriate stimulus. For example, under conditions of high osmolarity Ste11 can lead to activation of Hog1 but does not induce mating-specific genes. Conversely, conditions that activate the filamentation pathway (which utilizes STE11 and STE7) induce only genes that regulate filamentous growth without triggering pheromone responses or responses to high osmolarity. These observations suggest that yeast cells have developed efficient mechanisms to generate pathway specificity and to successfully suppress cross talk, even when individual components participate in more than one signaling pathway. FIG. 2 Scaffold and adapter molecules in MAPK pathways. MAPK scaffolds and adapters (gray shading) are thought to promote the formation of oligomeric protein complexes with components that function in a specific MAPK module. Scaffolds have been identified in ... In metazoan cells the problem is more complex because each cell is simultaneously exposed to multiple extracellular signals and must integrate these inputs to choose an appropriate response. Thus, the biological context of a signal plays a determinative role in the way that MAPK activation is interpreted. For example, although ERKs generally regulate cell growth and cell differentiation and JNKs participate in a stress response, this is not always the case and in certain cell types activation of JNKs can induce proliferation (110). This indicates that in mammalian systems physiologic responses associated with a certain MAPK module can be cell type specific. Moreover, in PC12 cells, transient stimulation of the ERK cascade leads to proliferation whereas sustained stimulation leads to differentiation,
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“Four main MAPK cascades have been identified: ERK1/2 (extracellular signal-regulated kinases), c-Jun N-terminal kinases (JNK), p38 (p38 kinase), and the BMK1/ERK5 (big MAP kinase 1) (Schaeffer and Weber 1999).”
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Cites
Marshall, C. J. (1995) · Cell · doi:10.1016/0092-8674(95)90401-8 · Cited by 3,906
Dérijard, B., Hibi, M., Wu, I.-H., Barrett, T., Su, B., Deng, T., Karin, M., & Davis, R. J. (1994) · Cell · doi:10.1016/0092-8674(94)90380-8 · Cited by 3,188
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 2,489
Signaling Through Scaffold, Anchoring, and Adaptor Proteins
Pawson, T., & Scott, J. D. (1997) · Science · doi:10.1126/science.278.5346.2075 · Cited by 2,256
Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP
de Rooij, J., Zwartkruis, F. J. T., Verheijen, M. H. G., Cool, R. H., Nijman, S. M. B., Wittinghofer, A., & Bos, J. L. (1998) · Nature · doi:10.1038/24884 · Cited by 1,970
Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase
Kato, S., Endoh, H., Masuhiro, Y., Kitamoto, T., Uchiyama, S., Sasaki, H., Masushige, S., Gotoh, Y., Nishida, E., Kawashima, H., et al. (1995) · Science · doi:10.1126/science.270.5241.1491 · Cited by 1,964
Cowley, S. A. (1994) · Cell · doi:10.1016/0092-8674(94)90133-3 · Cited by 1,959
Mammalian Ras interacts directly with the serine/threonine kinase raf
Vojtek, A. B., Hollenberg, S. M., & Cooper, J. A. (1993) · Cell · doi:10.1016/0092-8674(93)90307-c · Cited by 1,934
Knighton, D. R., Zheng, J., Eyck, L. F. T., Ashford, V. A., Xuong, N., Taylor, S. S., & Sowadski, J. M. (1991) · Science · doi:10.1126/science.1862342 · Cited by 1,764
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 1,759
Signal transduction by the c-Jun N-terminal kinase (JNK) — from inflammation to development
Ip, Y. T., & Davis, R. J. (1998) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(98)80143-9 · Cited by 1,538
Transcription Factor ATF2 Regulation by the JNK Signal Transduction Pathway
Gupta, S., Campbell, D., Dérijard, B., & Davis, R. J. (1995) · Science · doi:10.1126/science.7824938 · Cited by 1,433
Selective interaction of JNK protein kinase isoforms with transcription factors.
Gupta, S., Barrett, T., Whitmarsh, A. J., Cavanagh, J., Sluss, H. K., Dérijard, B., & Davis, R. J. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00636.x · Cited by 1,341
Raingeaud, J., Whitmarsh, A. J., Barrett, T., Dérijard, B., & Davis, R. J. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.3.1247 · Cited by 1,280
Raf-1 activates MAP kinase-kinase
Kyriakis, J. M., App, H., Zhang, X., Banerjee, P. T., Brautigan, D. L., Rapp, U. R., & Avruch, J. (1992) · Nature · doi:10.1038/358417a0 · Cited by 1,263
Identification of a signal for rapid export of proteins from the nucleus
Wen, W., Meinkotht, J. L., Tsien, R. Y., & Taylor, S. S. (1995) · Cell · doi:10.1016/0092-8674(95)90435-2 · Cited by 1,190
Exportin 1 (Crm1p) Is an Essential Nuclear Export Factor
Stade, K., Ford, C. S., Guthrie, C., & Weis, K. (1997) · Cell · doi:10.1016/s0092-8674(00)80370-0 · Cited by 1,145
Nuclear Localization and Regulation of erk- and rsk-Encoded Protein Kinases
Chen, R., Sarnecki, C., & Blenis, J. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.3.915 · Cited by 1,099
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
cAMP Activates MAP Kinase and Elk-1 through a B-Raf- and Rap1-Dependent Pathway
Vossler, M. R., Yao, H. W., York, R. D., Pan, M., Rim, C. S., & Stork, P. A. (1997) · Cell · doi:10.1016/s0092-8674(00)80184-1 · Cited by 1,044
Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane
Leevers, S. J., Paterson, H. F., & Marshall, C. J. (1994) · Nature · doi:10.1038/369411a0 · Cited by 1,011
Deák, M., Clifton, A. D., Lucocq, J. M., & Alessi, D. R. (1998) · The EMBO Journal · doi:10.1093/emboj/17.15.4426 · Cited by 1,004
MAP kinase pathways in yeast: For mating and more
Herskowitz, I. (1995) · Cell · doi:10.1016/0092-8674(95)90402-6 · Cited by 995
Complexes of Ras⋅GTP with Raf-1 and Mitogen-Activated Protein Kinase Kinase
Moodie, S. A., Willumsen, B. M., Weber, M. J., & Wolfman, A. (1993) · Science · doi:10.1126/science.8503013 · Cited by 968
Self-citationMitogen‐activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2
Waskiewicz, A. J., Flynn, A., Proud, C. G., & Cooper, J. A. (1997) · The EMBO Journal · doi:10.1093/emboj/16.8.1909 · Cited by 951
Inhibition by cAMP of Ras-Dependent Activation of Raf
Cook, S. J., & McCormick, F. P. (1993) · Science · doi:10.1126/science.7694367 · Cited by 942
Inhibition of the EGF-Activated MAP Kinase Signaling Pathway by Adenosine 3′,5′-Monophosphate
Wu, J., Dent, P., Jelı́nek, T., Wolfman, A., Weber, M. J., & Sturgill, T. W. (1993) · Science · doi:10.1126/science.7694366 · Cited by 919
Self-citationNormal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1
Zhang, X., Settleman, J. E., Kyriakis, J. M., Takeuchi-Suzuki, E., Elledge, S. J., Marshall, M. S., Bruder, J. T., Rapp, U. R., & Avruch, J. (1993) · Nature · doi:10.1038/364308a0 · Cited by 859
Rap1 mediates sustained MAP kinase activation induced by nerve growth factor
York, R. D., Yao, H. W., Dillon, T. J., Ellig, C. L., Eckert, S. P., McCleskey, E. W., & Stork, P. A. (1998) · Nature · doi:10.1038/33451 · Cited by 858
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
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
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
Phosphorylation of the MAP Kinase ERK2 Promotes Its Homodimerization and Nuclear Translocation
Khokhlatchev, A. V., Canagarajah, B. J., Wilsbacher, J. L., Robinson, M. J., Atkinson, M. A., Goldsmith, E. J., & Cobb, M. H. (1998) · Cell · doi:10.1016/s0092-8674(00)81189-7 · Cited by 675
Activation of Mitogen-Activated Protein Kinase Kinase by v-Raf in NIH 3T3 Cells and in Vitro
Dent, P., Haser, W. G., Haystead, T., Vincent, L. A., Roberts, T. M., & Sturgill, T. W. (1992) · Science · doi:10.1126/science.1326789 · Cited by 668
Fukunaga, R., & Hunter, T. (1997) · The EMBO Journal · doi:10.1093/emboj/16.8.1921 · Cited by 666
ERK phosphorylation potentiates Elk‐1‐mediated ternary complex formation and transactivation.
Gille, H., Kortenjann, M., Thomae, O., Moomaw, C. R., Slaughter, C. A., Cobb, M. H., & Shaw, P. E. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07076.x · Cited by 665
Lenormand, P., Sardet, C., Pagès, G., L’Allemain, G., Brunet, A., & Pouysségur, J. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.122.5.1079 · Cited by 660
Multiple ras functions can contribute to mammalian cell transformation
White, M. A., Nicolette, C. A., Minden, A., Polverino, A. J., Aelst, L. V., Karin, M., & Wigler, M. H. (1995) · Cell · doi:10.1016/0092-8674(95)90507-3 · Cited by 653
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
Kallunki, T., Su, B., Tsigelny, I., Sluss, H. K., Dérijard, B., Moore, G., Davis, R., & Karin, M. (1994) · Genes & Development · doi:10.1101/gad.8.24.2996 · Cited by 642
Complex formation between RAS and RAF and other protein kinases.
Aelst, L. V., Barr, M. M., Marcus, S., Polverino, A. J., & Wigler, M. H. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.13.6213 · Cited by 620
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
Defective T Cell Differentiation in the Absence of Jnk1
Dong, C., Yang, D. D., Wysk, M., Whitmarsh, A. J., Davis, R. J., & Flavell, R. A. (1998) · Science · doi:10.1126/science.282.5396.2092 · Cited by 579
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
Songyang, Z., Lu, K. P., Kwon, Y. T., Tsai, L., Filhol, O., Cochet, C., Brickey, D. A., Soderling, T. R., Bartleson, C., Graves, D. J., et al. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.11.6486 · Cited by 550
Coordination of Three Signaling Enzymes by AKAP79, a Mammalian Scaffold Protein
Klauck, T. M., Faux, M. C., Labudda, K., Langeberg, L. K., Jaken, S., & Scott, J. D. (1996) · Science · doi:10.1126/science.271.5255.1589 · Cited by 547
David, M., Petricoin, E., Benjamin, C. D., Pine, R. I., Weber, M. J., & Larner, A. C. (1995) · Science · doi:10.1126/science.7569900 · Cited by 543
Self-citationInduction of c‐fos expression through JNK‐mediated TCF/Elk‐1 phosphorylation.
Cavigelli, M., Dolfi, F., Claret, F. X., & Karin, M. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00284.x · Cited by 530
Ste5 tethers multiple protein kinases in the MAP kinase cascade required for mating in S. cerevisiae
Chol, K.-Y., Satterberg, B., Lyons, D. M., & Elion, E. A. (1994) · Cell · doi:10.1016/0092-8674(94)90427-8 · Cited by 502
c-Jun Can Recruit JNK to Phosphorylate Dimerization Partners via Specific Docking Interactions
Kallunki, T., Deng, T., Hibi, M., & Karin, M. (1996) · Cell · doi:10.1016/s0092-8674(00)81999-6 · Cited by 492
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
Self-citationThe 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
Chu, Y., Solski, P. A., Khosravi‐Far, R., Der, C. J., & Kelly, K. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.11.6497 · Cited by 442
Madhani, H. D., Styles, C. A., & Fink, G. R. (1997) · Cell · doi:10.1016/s0092-8674(00)80454-7 · Cited by 428
Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin β homologs NMD5 and XPO1
Ferrigno, P. K., Posas, F., Koepp, D. M., Saito, H., & Silver, P. A. (1998) · The EMBO Journal · doi:10.1093/emboj/17.19.5606 · Cited by 417
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
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
Clark‐Lewis, I., Sanghera, J. S., & Pelech, S. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)98601-1 · Cited by 400
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 394
Structural organization of MAP-kinase signaling modules by scaffold proteins in yeast and mammals
Whitmarsh, A. J., & Davis, R. J. (1998) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01309-7 · Cited by 387
Fukuda, M., Gotoh, Y., & Nishida, E. (1997) · The EMBO Journal · doi:10.1093/emboj/16.8.1901 · Cited by 385
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
Increasing cAMP attenuates activation of mitogen-activated protein kinase.
Sevetson, B. R., Kong, X., & Lawrence, J. C. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.21.10305 · Cited by 366
Association of mitogen-activated protein kinase with the microtubule cytoskeleton.
Reszka, A. A., Seger, R., Diltz, C. D., Krebs, E. G., & Fischer, E. H. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.19.8881 · Cited by 364
Nuclear Accumulation of NFAT4 Opposed by the JNK Signal Transduction Pathway
Chow, C.-W., Rincón, M., Cavanagh, J., Dickens, M., & Davis, R. J. (1997) · Science · doi:10.1126/science.278.5343.1638 · Cited by 357
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
Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2
Ben-Levy, R., Hooper, S., Wilson, R., Paterson, H. F., & Marshall, C. J. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70442-7 · Cited by 338
Differential regulation of c‐Jun by ERK and JNK during PC12 cell differentiation
Leppä, S., Saffrich, R., Ansorge, W., & Bohmann, D. (1998) · The EMBO Journal · doi:10.1093/emboj/17.15.4404 · Cited by 332
Printen, J. A., & Sprague, G. F. (1994) · Genetics · doi:10.1093/genetics/138.3.609 · Cited by 329
Cyclic AMP activates the mitogen-activated protein kinase cascade in PC12 cells.
Frödin, M., Peraldi, P., & Obberghen‐Schilling, E. V. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37589-0 · Cited by 326
Yujiri, T. (1998) · Science · doi:10.1126/science.282.5395.1911 · Cited by 326
Fukuda, M., Gotoh, I., Gotoh, Y., & Nishida, E. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.33.20024 · Cited by 325
González, F. M., Seth, A., Raden, D. L., Bowman, D., Fay, F., & Davis, R. J. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.122.5.1089 · Cited by 320
Differential targeting of MAP kinases to the ETS‐domain transcription factor Elk‐1
Yang, S., Whitmarsh, A. J., Davis, R. J., & Sharrocks, A. D. (1998) · The EMBO Journal · doi:10.1093/emboj/17.6.1740 · Cited by 299
Growth factor activation of MAP kinase requires cell adhesion
Renshaw, M. W., Ren, X., & Schwartz, M. A. (1997) · The EMBO Journal · doi:10.1093/emboj/16.18.5592 · Cited by 296
The riddle of MAP kinase signaling specificity
Madhani, H. D., & Fink, G. R. (1998) · Trends in Genetics · doi:10.1016/s0168-9525(98)01425-5 · Cited by 293
Leptomycin B‐sensitive nuclear export of MAPKAP kinase 2 is regulated by phosphorylation
Engel, K., Kotlyarov, A., & Gaestel, M. (1998) · The EMBO Journal · doi:10.1093/emboj/17.12.3363 · Cited by 266
Activation of the Protein Kinase p38 in the Spindle Assembly Checkpoint and Mitotic Arrest
Takenaka, K., Moriguchi, T., & Nishida, E. (1998) · Science · doi:10.1126/science.280.5363.599 · Cited by 263
Nagata, K., Puls, A., Futter, C. E., Aspenstrom, P., Schaefer, E., Nakata, T., Hirokawa, N., & Hall, A. (1998) · The EMBO Journal · doi:10.1093/emboj/17.1.149 · Cited by 263
Cook, J. G., Bardwell, L., & Thorner, J. W. (1997) · Nature · doi:10.1038/36355 · Cited by 258
Errede, B., & Ammerer, G. (1989) · Genes & Development · doi:10.1101/gad.3.9.1349 · Cited by 256
Marcus, S., Polverino, A. J., Barr, M. M., & Wigler, M. H. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.16.7762 · Cited by 242
Erickson, A. K., Payne, D. M., Martino, P. A., Rossomando, A. J., Shabanowitz, J., Weber, M. J., Hunt, D. F., & Sturgill, T. W. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)45433-0 · Cited by 239
Self-citationThe Ras signaling pathway in Drosophila
Wassarman, D. A., Therrien, M., & Rubin, G. M. (1995) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(95)90052-7 · Cited by 233
Shapiro, P. S., Vaisberg, E. A., Hunt, A. J., Tolwinski, N. S., Whalen, A. M., McIntosh, J. R., & Ahn, N. G. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.6.1533 · Cited by 224
Cook, J. G., Bardwell, L., Kron, S. J., & Thorner, J. W. (1996) · Genes & Development · doi:10.1101/gad.10.22.2831 · Cited by 221
Zečević, M., Catling, A. D., Eblen, S. T., Renzi, L., Hittle, J. C., Yen, T. J., Gorbsky, G. J., & Weber, M. J. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.6.1547 · Cited by 219
Self-citationExtracellular signal‐regulated activation of Rap1 fails to interfere in Ras effector signalling
Zwartkruis, F. J. T., Wolthuis, R. M. F., Nabben, N. M. J. M., Franke, B., & Bos, J. L. (1998) · The EMBO Journal · doi:10.1093/emboj/17.20.5905 · Cited by 218
Xia, Y., Wu, Z., Su, B., Murray, B. W., & Karin, M. (1998) · Genes & Development · doi:10.1101/gad.12.21.3369 · Cited by 203
Regulation of the MAP kinase pathway by mammalian Ksr through direct interaction with MEK and ERK
Yu, W., Fantl, W. J., Harrowe, G., & Williams, L. T. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70020-x · Cited by 197
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
Self-citationMinden, A., Lin, A., Smeal, T., Dérijard, B., Cobb, M., Davis, R., & Karin, M. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.10.6683 · Cited by 195
Activation of ternary complex factor Elk-1 by stress-activated protein kinases
Gille, H., Strahl, T., & Shaw, P. E. (1995) · Current Biology · doi:10.1016/s0960-9822(95)00235-1 · Cited by 192
Tedford, K., Kim, S., Sa, D., Stevens, K., & Tyers, M. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00118-7 · Cited by 191
Jaaro, H., Rubinfeld, H., Hanoch, T., & Seger, R. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3742 · Cited by 182
A Novel Regulatory Mechanism in the Mitogen-activated Protein (MAP) Kinase Cascade
Fukuda, M., Gotoh, I., Adachi, M., Gotoh, Y., & Nishida, E. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.51.32642 · Cited by 182
Corbalán‐García, S., Yang, S., Degenhardt, K., & Bar‐Sagi, D. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.10.5674 · Cited by 181
Bardwell, L., Cook, J. G., Voora, D., Baggott, D. M., Martinez, A. R., & Thorner, J. W. (1998) · Genes & Development · doi:10.1101/gad.12.18.2887 · Cited by 180
Ludwig, S., Engel, K., Hoffmeyer, A., Sithanandam, G., Neufeld, B., Palm, D., Gaestel, M., & Rapp, U. R. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.12.6687 · Cited by 177
Moore, M. S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.36.22857 · Cited by 175
Haystead, T., Weiel, J. E., Litchfield, D. W., Tsukitani, Y., Fischer, E. H., & Krebs, E. G. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)46261-2 · Cited by 173
The protein kinase KSR interacts with 14-3-3 protein and Raf
Xing, H., Kornfeld, K., & Muslin, A. J. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00152-7 · Cited by 173
EGF induced SOS phosphorylation in PC12 cells involves P90 RSK-2
Douville, E., & Downward, J. (1997) · Oncogene · doi:10.1038/sj.onc.1201214 · Cited by 165
Saccharomyces cerevisiae TEC1 is required for pseudohyphal growth
Gavrias, V., Andrianopoulos, A., Gimeno, C. J., & Timberlake, W. E. (1996) · Molecular Microbiology · doi:10.1111/j.1365-2958.1996.tb02470.x · Cited by 165
Xu, S., Robbins, D. J., Frost, J. A., Dang, A., Lange, C. A., & Cobb, M. H. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.15.6808 · Cited by 157
Bokemeyer, D., Sorokin, A., Yan, M., Ahn, N. G., Templeton, D. J., & Dunn, M. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.2.639 · Cited by 157
Brondello, J., McKenzie, F. R., Sun, H., Tonks, N. K., & Pouysségur, J. (1995) · PubMed · Cited by 154
Kockel, L., Zeitlinger, J., Staszewski, L. M., Mlodzik, M., & Bohmann, D. (1997) · Genes & Development · doi:10.1101/gad.11.13.1748 · Cited by 152
The pool of map kinase associated with microtubules is small but constitutively active.
Morishima‐Kawashima, M., & Kosik, K. S. (1996) · Molecular Biology of the Cell · doi:10.1091/mbc.7.6.893 · Cited by 141
Melchior, F., & Gerace, L. (1998) · Trends in Cell Biology · doi:10.1016/s0962-8924(98)01252-5 · Cited by 140
Erhardt, P., Troppmair, J., Rapp, U. R., & Cooper, G. M. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.10.5524 · Cited by 139
Bardwell, L., Cook, J. G., Zhu-Shimoni, J. X., Voora, D., & Thorner, J. W. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15400 · Cited by 138
Hagen, D. C., McCaffrey, G., & Sprague, G. F. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.6.2952-2961.1991 · Cited by 132
Identification of MAP Kinase Domains by Redirecting Stress Signals into Growth Factor Responses
Brunet, A., & Pouysségur, J. (1996) · Science · doi:10.1126/science.272.5268.1652 · Cited by 125
Young, S. W., Dickens, M., & Tavaré, J. M. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)80367-6 · Cited by 124
Wu, X., Noh, S. J., Zhou, G., Dixon, J. E., & Guan, K. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.6.3265 · Cited by 119
RAS and RAF-1 Form a Signalling Complex with MEK-1 but Not MEK-2
Jelı́nek, T., Catling, A. D., Reuter, C. W., Moodie, S. A., Wolfman, A., & Weber, M. J. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.12.8212 · Cited by 119
Self-citationTreier, M., Bohmann, D., & Mlodzik, M. (1995) · Cell · doi:10.1016/0092-8674(95)90188-4 · Cited by 116
Ste12 and Mcm1 Regulate Cell Cycle-Dependent Transcription of FAR1
Oehlen, L. J. W. M., McKinney, J. D., & Cross, F. R. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.6.2830 · Cited by 113
Chen, T., Cho, R. W., Stork, P. A., & Weber, M. J. (1999) · PubMed · Cited by 106
Self-citationA Role for Mitogen-activated Protein Kinase in the Spindle Assembly Checkpoint in XTC Cells
Wang, X. M., Zhai, Y., & Ferrell, J. E. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.2.433 · Cited by 104
Papin, C., Denouel-Galy, A., Laugier, D., Calothy, G., & Eychène, A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.38.24939 · Cited by 101
Rossomando, A. J., Dent, P., Sturgill, T. W., & Marshak, D. R. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.3.1594 · Cited by 100
Mansour, S. J., Resing, K. A., Candi, J. M., Hermann, A. S., Gloor, J. W., Herskind, K. R., Wartmann, M., Davis, R. J., & Ahn, N. G. (1994) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a124524 · Cited by 98
Ueki, K., Matsuda, S., Tobe, K., Gotoh, Y., Tamemoto, H., Yachi, M., Akanuma, Y., Yazaki, Y., Nishida, E., & Kadowaki, T. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)40745-9 · Cited by 97
Nucleocytoplasmic transport: Driving and directing transport
Cole, C. N., & Hammell, C. M. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70239-8 · Cited by 96
Requirement for MAPK Activation for Normal Mitotic Progression in Xenopus Egg Extracts
Guadagno, T. M., & Ferrell, J. E. (1998) · Science · doi:10.1126/science.282.5392.1312 · Cited by 93
Properties of the DNA-Binding Domain of the Saccharomyces cerevisiae STE12 Protein
Yuan, Y.-L. O., & Fields, S. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.12.5910-5918.1991 · Cited by 82
Identification of signalling proteins interacting with B-Raf in the yeast two-hybrid system.
Papin, C., DENOUEL, A., Calothy, G., & Eychène, A. (1996) · PubMed · Cited by 76
The Dictyostelium MAP kinase ERK2 regulates multiple, independent developmental pathways.Preprint
Gaskins, C. J., Clark, A. M., Aubry, L., Segall, J. E., & Firtel, R. (1996) · Genes & Development · doi:10.1101/gad.10.1.118 · Cited by 73
A role for JNK/SAPK in proliferation, but not apoptosis, of IL-3-dependent cells
Smith, A., Ramos‐Morales, F., Ashworth, A., & Collins, M. K. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00380-0 · Cited by 71
Dang, A., Frost, J. A., & Cobb, M. H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.31.19909 · Cited by 69
Anchoring and scaffold proteins for kinases and phosphatases.
Lester, L. B., & Scott, J. D. (1997) · PubMed · Cited by 68
Control and integration of cell signaling pathways during C. Elegans vulval development
Sundaram, M. V., & Han, M. (1996) · BioEssays · doi:10.1002/bies.950180609 · Cited by 68
Shapiro, P. S., & Ahn, N. G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.3.1788 · Cited by 68
Yeast MEK-Dependent Signal Transduction: Response Thresholds and Parameters Affecting Fidelity
Yashar, B. M., Irie, K., Printen, J. A., Stevenson, B. J., Sprague, G. F., Matsumoto, K., & Errede, B. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.12.6545 · Cited by 68
Casillas, A. M., Amaral, K. C., Chegini-Farahani, S., & Nel, A. E. (1993) · Biochemical Journal · doi:10.1042/bj2900545 · Cited by 58
Phosphorylation of Drosophila Jun by the MAP kinase rolled regulates photoreceptor differentiation.
Peverali, F. A., Isaksson, A., Papavassiliou, A. G., Plastina, P., Staszewski, L. M., Mlodzik, M., & Bohmann, D. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00768.x · Cited by 55
Chung, C. Y., Reddy, T. B. K., Zhou, K., & Firtel, R. (1998) · Genes & Development · doi:10.1101/gad.12.22.3564 · Cited by 53
Lewis, T., Groom, L. A., Sneddon, A. A., Smythe, C., & Keyse, S. M. (1995) · Journal of Cell Science · doi:10.1242/jcs.108.8.2885 · Cited by 42
B-Raf protein isoforms interact with and phosphorylate Mek-1 on serine residues 218 and 222.
Papin, C., Eychène, A., Brunet, A., Pagès, G., Pouysségur, J., Calothy, G., & Barnier, J. (1995) · PubMed · Cited by 41
Amaral, M., Casillas, A. M., & Nel, A. E. (1993) · PubMed Central · Cited by 36
Feedback regulation of map kinase signal pathways
Errede, B., Ge, Q., Karin, M., & Marshall, C. J. (1996) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.1996.0010 · Cited by 35
Dissection of protein kinase and phosphatase targeting interactions.
Scott, J. D. (1997) · PubMed · Cited by 35
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Signal transduction by the JNK group of MAP kinases
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Dhillon, A. S., Hagan, S., Rath, O., & Kolch, W. (2007) · Oncogene · doi:10.1038/sj.onc.1210421 · Cited by 2,995
“…six distinct groups of MAPKs have been characterized in mammals; extracellular signal-regulated kinase (ERK)1/2, ERK3/ 4, ERK5, ERK7/8, Jun N-terminal kinase (JNK)1/2/3 and the p38 isoforms a/b/g(ERK6)/d (Schaeffer and Weber, 1999; Chen et al., 2001b; Kyriakis and Avruch, 2001; Krens et al., 2006).”
BackgroundReactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
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“[90] L. Resnick, M. Fennell, Targeting JNK3 for the treatment of neurodegenerative disorders, Drug Discov.”
Background
Metadata
- Authors
- Schaeffer, H. J., & Weber, M. J.
- Affiliations
- University of Virginia (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1999-04
- Volume
- 19
- Issue
- 4
- Pages
- 2435-2444
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC84036
- OpenAlex
- W1899552864
- Semantic Scholar
- bf5b29dd374f8bafd23fa8c6a133d764aa27c83f
- Cited by
- 1,600
- References
- 144
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 24 · 2023: 32 · 2022: 23 · 2021: 28 · 2020: 19 · 2019: 37 · 2018: 43 · 2017: 27 · 2016: 31 · 2015: 41 · 2014: 42 · 2013: 49 · 2012: 61
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01gm047332-08, 1r01ca076500-01a1)
- U.S. Public Health Service
- National Cancer Institute (CA-39076, CA76500)
- National Institute of General Medical Sciences (GM-47332)
- 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 › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- mitogen-activated protein kinase, MAPK signaling, signal transduction, ERK1/2, JNK, p38 MAPK, adaptor proteins, Saccharomyces cerevisiae, cell differentiation, stress response, apoptosis, cell growth and division
- MeSH terms
- Carrier Proteins, Cell Compartmentation, Fungal Proteins, Models, Biological, Morphogenesis, Protein Kinases, Saccharomyces cerevisiae, Substrate Specificity, Time Factors, Signal Transduction, Calcium-Calmodulin-Dependent Protein Kinases, Receptor Cross-Talk, Mitogen-Activated Protein Kinase Kinases, Saccharomyces cerevisiae Proteins, Adaptor Proteins, Signal Transducing
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