JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation.
Open accessAbstract
The transcriptional activity of c-Jun is augmented through phosphorylation at two sites by a c-Jun amino-terminal kinase (JNK). All cells express two distinct JNK activities, 46 and 55 kD in size. It is not clear which of them is the more important c-Jun kinase and how they specifically recognize c-Jun. The 46-kD form of JNK was identified as a new member of the MAP kinase group of signal-transducing enzymes, JNK1. Here, we report the molecular cloning of the 55-kD form of JNK, JNK2, which exhibits 83% identity and similar regulation to JNK1. Despite this close similarity, the two JNKs differ greatly in their ability to interact with c-Jun. JNK2 binds c-Jun approximately 25 times more efficiently than JNK1, and as a result has a lower Km toward c-Jun than JNK1. The structural basis for this difference was investigated and traced to a small beta-strand-like region near the catalytic pocket of the enzyme. Modeling suggests that this region is solvent exposed and therefore is likely to serve as a docking site that increases the effective concentration of c-Jun near JNK2. These results explain how two closely related MAP kinases can differ in their ability to recognize specific substrates and thereby elicit different biological responses.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
MAPKs contain a docking site in the C-terminal lobe that binds a conserved 13-16 amino acid sequence known as the D- or KIM-motif.
“Almost 20 years ago, it was discovered that MAPKs contain a docking site in the C-terminal lobe that binds a conserved 13-16 amino acid sequence known as the D-or KIM-motif (kinase interaction motif).”
From Molecular basis of MAP kinase regulation (2013) · cites this paper as [19]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Protein Kinase Family: Conserved Features and Deduced Phylogeny of the Catalytic Domains
Hanks, S. K., Quinn, A. M., & Hunter, T. R. (1988) · Science · doi:10.1126/science.3291115 · Cited by 5,040 · see citing works
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 · see citing works
Self-citationThe stress-activated protein kinase subfamily of c-Jun kinases
Kyriakis, J. M., Banerjee, P. T., Nikolakaki, E., Dai, T., Rubie, E. A., Ahmad, M. F., Avruch, J., & Woodgett, J. R. (1994) · Nature · doi:10.1038/369156a0 · Cited by 2,601 · see citing works
The mitogen-activated protein kinase signal transduction pathway
Davis, R. J. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82362-6 · Cited by 2,112 · see citing works
Self-citationHibi, M., Lin, A., Smeal, T., Minden, A., & Karin, M. (1993) · Genes & Development · doi:10.1101/gad.7.11.2135 · Cited by 1,886 · see citing works
Self-citationBoulton, T. G., Nye, S. H., Robbins, D. J., Ip, N. Y., Radzlejewska, E., Morgenbesser, S. D., DePinho, R. A., Panayotatos, N., Cobb, M. H., & Yancopoulos, G. D. (1991) · Cell · doi:10.1016/0092-8674(91)90098-j · Cited by 1,876 · see citing works
Phosphorylation of c-jun mediated by MAP kinases
Pulverer, B., Kyriakis, J. M., Avruch, J., Nikolakaki, E., & Woodgett, J. R. (1991) · Nature · doi:10.1038/353670a0 · Cited by 1,470 · see citing works
Boyle, W. J., van der Geer, P., & Hunter, T. R. (1991) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(91)01013-r · Cited by 1,452 · see citing works
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 1,440 · see citing works
Self-citationThe jun proto-oncogene is positively autoregulated by its product, Jun/AP-1
Angel, P., Hattori, K., Smeal, T., & Karin, M. (1988) · Cell · doi:10.1016/0092-8674(88)90143-2 · Cited by 1,239 · see citing works
Self-citationCrystal 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
JNK is involved in signal integration during costimulation of T lymphocytes
Su, B., Jacinto, E., Hibi, M., Kallunki, T., Karin, M., & Ben‐Neriah, Y. (1994) · Cell · doi:10.1016/0092-8674(94)90056-6 · Cited by 907 · see citing works
Self-citationThe mammalian ultraviolet response is triggered by activation of src tyrosine kinases
Devary, Y., Gottlieb, R. A., Smeal, T., & Karin, M. (1992) · Cell · doi:10.1016/s0092-8674(05)80058-3 · Cited by 852 · see citing works
Self-citationThe structure of an antigenic determinant in a protein
Wilson, I. A., Niman, H. L., Houghten, R. A., Cherenson, A. R., Connolly, M. L., & Lerner, R. A. (1984) · Cell · doi:10.1016/0092-8674(84)90412-4 · Cited by 829 · see citing works
Smeal, T., Binetruy, B., Mercola, D. A., Birrer, M., & Karin, M. (1991) · Nature · doi:10.1038/354494a0 · Cited by 789 · see citing works
Self-citationAn Insulin-Stimulated Protein Kinase Similar to Yeast Kinases Involved in Cell Cycle Control
Boulton, T. G., Yancopoulos, G. D., Gregory, J. S., Slaughter, C. A., Moomaw, C. R., Hsu, J., & Cobb, M. H. (1990) · Science · doi:10.1126/science.2164259 · Cited by 707 · see citing works
O'Neill, E. M., Rebay, I., Tjian, R., & Rubin, G. M. (1994) · Cell · doi:10.1016/0092-8674(94)90580-0 · Cited by 675 · see citing works
Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain
Binétruy, B., Smeal, T., & Karin, M. (1991) · Nature · doi:10.1038/351122a0 · Cited by 598 · see citing works
Self-citationAtomic 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
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
Alvarez, E., Northwood, I. C., Gonzalez, F. A., Latour, D. A., Seth, A., Abate, C., Curran, T., & Davis, R. J. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)98613-8 · Cited by 472 · see citing works
Self-citationMinden, A., Lin, A., Smeal, T., Dérijard, B., Cobb, M. H., Davis, R. J., & Karin, M. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.10.6683 · Cited by 467 · see citing works
Self-citationKameshita, I., & Fujisawa, H. (1989) · Analytical Biochemistry · doi:10.1016/0003-2697(89)90181-4 · Cited by 460 · see citing works
FUS3 encodes a cdc2+/CDC28-related kinase required for the transition from mitosis into conjugation
Elion, E. A., Grisafi, P. L., & Fink, G. R. (1990) · Cell · doi:10.1016/0092-8674(90)90668-5 · Cited by 433 · see citing works
Brunner, D., Oellers, N., Szabad, J., Biggs, W., Zipursky, S. L., & Hafen, E. (1994) · Cell · doi:10.1016/0092-8674(94)90362-x · Cited by 409 · see citing works
Karin, M. (1994) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(94)90035-3 · Cited by 394 · see citing works
Self-citationvan Dam, H., Duyndam, M., Rottier, R., Bosch, A., de Vries‐Smits, L., Herrlich, P., Zantema, A., Angel, P., & van der Eb, A. J. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05680.x · Cited by 375 · see citing works
Smeal, T., Binétruy, B., Mercola, D., Grover-Bardwick, A., Heidecker, G., Rapp, U. R., & Karin, M. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.8.3507 · Cited by 335 · see citing works
Self-citationCano, E., Hazzalin, C. A., & Mahadevan, L. C. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.11.7352 · Cited by 297 · see citing works
The mitogen-activated protein kinase activator
Ahn, N. G., Seger, R., & Krebs, E. G. (1992) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(92)90131-u · Cited by 284 · see citing works
Edwards, D. R., & Mahadevan, L. C. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05306.x · Cited by 280 · see citing works
Elion, E. A., Satterberg, B., & Kranz, J. E. (1993) · Molecular Biology of the Cell · doi:10.1091/mbc.4.5.495 · Cited by 268 · see citing works
Kurjan, J. (1992) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.61.070192.005313 · Cited by 203 · see citing works
Sex, stress and integrity: the importance of MAP kinases in yeast
Ammerer, G. (1994) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(94)90096-5 · Cited by 74 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cell Signaling by Receptor Tyrosine Kinases
Lemmon, M. A., & Schlessinger, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.011 · Cited by 7,929 · see citing works
Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis
Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J., & Greenberg, M. E. (1995) · Science · doi:10.1126/science.270.5240.1326 · Cited by 5,290 · see citing works
Self-citationSignal transduction by the JNK group of MAP kinases
Davis, R. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00116-1 · Cited by 4,237 · see citing works
Self-citationMitogen-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 4,044 · see citing works
Cell Signaling by Receptor Tyrosine Kinases
Schlessinger, J. (2000) · Cell · doi:10.1016/s0092-8674(00)00114-8 · Cited by 3,774 · see citing works
Kyriakis, J. M., & Avruch, J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.807 · Cited by 3,369 · see citing works
Karin, M., Liu, Z.-G., & Zandi, E. (1997) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(97)80068-3 · Cited by 2,904 · see citing works
Self-citationMitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human
Widmann, C., Gibson, S. B., Jarpe, M. B., & Johnson, G. L. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.1.143 · Cited by 2,707 · see citing works
Hunter, T. (2000) · Cell · doi:10.1016/s0092-8674(00)81688-8 · Cited by 2,586 · see citing works
SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase
Bennett, B. L., Sasaki, D. T., Murray, B. W., O'Leary, E. C., Sakata, S. T., Xu, W., Leisten, J. C., Motiwala, A., Pierce, S., Satoh, Y., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251194298 · Cited by 2,558 · see citing works
The Regulation of AP-1 Activity by Mitogen-activated Protein Kinases
Karin, M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.28.16483 · Cited by 2,432 · see citing works
Self-citationRaingeaud, 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
Self-citationA cytokine-responsive IκB kinase that activates the transcription factor NF-κB
DiDonato, J. A., Hayakawa, M., Rothwarf, D. M., Zandi, E., & Karin, M. (1997) · Nature · doi:10.1038/41493 · Cited by 2,125 · see citing works
Self-citationLiu, Z.-G., Hsu, H., Goeddel, D. V., & Karin, M. (1996) · Cell · doi:10.1016/s0092-8674(00)81375-6 · Cited by 1,937 · see citing works
Self-citationSignal Transduction through MAP Kinase Cascades
Lewis, T. S., Shapiro, P. S., & Ahn, N. G. (1998) · Advances in cancer research · doi:10.1016/s0065-230x(08)60765-4 · Cited by 1,746 · see citing works
Molecular targets of dietary agents for prevention and therapy of cancer
Aggarwal, B. B., & Shishodia, S. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.02.009 · Cited by 1,757 · see citing works
Mitogen-Activated Protein Kinases: Specific Messages from Ubiquitous Messengers
Schaeffer, H. J., & Weber, M. J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.4.2435 · Cited by 1,600 · see citing works
Whitmarsh, A. J., & Davis, R. J. (1996) · Journal of Molecular Medicine · doi:10.1007/s001090050063 · Cited by 1,543 · see citing works
Self-citationMechanisms of specificity in protein phosphorylation
Ubersax, J. A., & Ferrell Jr, J. E. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2203 · Cited by 1,451 · see citing works
Mammalian MAPK Signal Transduction Pathways Activated by Stress and Inflammation: A 10-Year Update
Kyriakis, J. M., & Avruch, J. (2012) · Physiological Reviews · doi:10.1152/physrev.00028.2011 · Cited by 1,476 · see citing works
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 1,440 · see citing works
Self-citationHerdegen, T., & Leah, J. D. (1998) · Brain Research Reviews · doi:10.1016/s0165-0173(98)00018-6 · Cited by 1,352 · see citing works
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 · see citing works
Self-citationRaingeaud, 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 · see citing works
Self-citationTranscriptional Regulation by Extracellular signals: Mechanisms and Specificity
Hill, C. S., & Treisman, R. (1995) · Cell · doi:10.1016/0092-8674(95)90403-4 · Cited by 1,263 · see citing works
Cyclin D1 Expression Is Regulated Positively by the p42/p44 and Negatively by the p38/HOG Pathway
Lavoie, J. N., L’Allemain, G., Brunet, A., Müller, R., & Pouysségur, J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.34.20608 · Cited by 1,210 · 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
Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARFPreprint
Jacobs, J. J. L., Scheijen, B., Voncken, J. W., Kieboom, K., Berns, A. J. M., & van Lohuizen, M. (1999) · Genes & Development · doi:10.1101/gad.13.20.2678 · Cited by 1,060 · see citing works
Rosette, C., & Karin, M. (1996) · Science · doi:10.1126/science.274.5290.1194 · Cited by 1,034 · see citing works
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 · see citing works
Cobb, M. H. (1999) · Progress in Biophysics and Molecular Biology · doi:10.1016/s0079-6107(98)00056-x · Cited by 869 · see citing works
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 790 · see citing works
Han, Z., Boyle, D. L., Chang, L., Bennett, B. L., Karin, M., Yang, L., Manning, A. M., & Firestein, G. S. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12466 · Cited by 781 · see citing works
Self-citationJaiswal, R. K., Jaiswal, N., Bruder, S. P., Mbalaviele, G., Marshak, D. R., & Pittenger, M. F. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.13.9645 · Cited by 771 · 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
Self-citationMitogen-activated protein kinase cascades and regulation of gene expression
Su, B., & Karin, M. (1996) · Current Opinion in Immunology · doi:10.1016/s0952-7915(96)80131-2 · Cited by 747 · see citing works
Self-citationKarin, M., & Hunter, T. R. (1995) · Current Biology · doi:10.1016/s0960-9822(95)00151-5 · Cited by 752 · see citing works
Self-citationCharacterization 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
Activation mechanism of the MAP kinase ERK2 by dual phosphorylation
Canagarajah, B. J., Khokhlatchev, A., Cobb, M. H., & Goldsmith, E. J. (1997) · Cell · doi:10.1016/s0092-8674(00)80351-7 · Cited by 729 · see citing works
Kasibhatla, S., Brunner, T., Genestier, L., Echeverri, F., Mahboubi, A., & Green, D. R. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80054-4 · Cited by 721 · see citing works
A Cytoplasmic Inhibitor of the JNK Signal Transduction Pathway
Dickens, M., Rogers, J. S., Cavanagh, J., Raitano, A., Xia, Z., Halpern, J. R., Greenberg, M. E., Sawyers, C. L., & Davis, R. J. (1997) · Science · doi:10.1126/science.277.5326.693 · Cited by 675 · see citing works
Self-citationHsp70 exerts its anti‐apoptotic function downstream of caspase‐3‐like proteases
Jäättelä, M., Wissing, D., Kokholm, K., Kallunki, T., & Egeblad, M. (1998) · The EMBO Journal · doi:10.1093/emboj/17.21.6124 · Cited by 679 · see citing works
Self-citationPhosphorylation 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 · see citing works
Fukunaga, R., & Hunter, T. (1997) · The EMBO Journal · doi:10.1093/emboj/16.8.1921 · Cited by 666 · see citing works
Kinetic and Catalytic Mechanisms of Protein Kinases
Adams, J. A. (2001) · Chemical Reviews · doi:10.1021/cr000230w · Cited by 630 · see citing works
Brunet, A., Roux, D., Lenormand, P., Dowd, S., Keyse, S. M., & Pouysségur, J. (1999) · The EMBO Journal · doi:10.1093/emboj/18.3.664 · Cited by 595 · see citing works
Ma, Q.-L., Yang, F., Rosario, E. R., Ubeda, O. J., Beech, W., Gant, D. J., Chen, P. P., Hudspeth, B., Chen, C., Zhao, Y., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1071-09.2009 · Cited by 536 · see citing works
Induction 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 · see citing works
Self-citationKeshet, Y., & Seger, R. (2010) · Methods in Molecular Biology · doi:10.1007/978-1-60761-795-2_1 · Cited by 642 · see citing works
JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships
Zeke, A., Misheva, M., Reményi, A., & Bogoyevitch, M. A. (2016) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00043-14 · Cited by 524 · see citing works
Stimulation of the Stress-Activated Mitogen-Activated Protein Kinase Subfamilies in Perfused Heart
Bogoyevitch, M. A., Brown, J. E., Ketterman, A. J., Fuller, S. J., Ben-Levy, R., Ashworth, A., Marshall, C. J., & Sugden, P. H. (1996) · Circulation Research · doi:10.1161/01.res.79.2.162 · Cited by 526 · see citing works
MEKK1/JNK signaling stabilizes and activates p53
Fuchs, S. Y., Adler, V., Pincus, M. R., & Ronai, Z. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10541 · Cited by 521 · see citing works
The c-Jun transcription factor – bipotential mediator of neuronal death, survival and regeneration
Herdegen, T., Skene, J. H. P., & Bähr, M. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)01000-4 · Cited by 524 · see citing works
The c-jun kinase/stress-activated pathway: Regulation, function and role in human disease
Johnson, G. L., & Nakamura, K. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.12.009 · Cited by 505 · see citing works
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 · see citing works
Self-citationMielke, K., & Herdegen, T. (2000) · Progress in Neurobiology · doi:10.1016/s0301-0082(99)00042-8 · Cited by 489 · see citing works
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
Regulation and function of the JNK subgroup of MAP kinases
Minden, A., & Karin, M. (1997) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(97)00018-8 · Cited by 486 · see citing works
Self-citationThe regulation of extracellular signal-regulated kinase (ERK) in mammalian cells
Ramos, J. W. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.04.009 · Cited by 477 · see citing works
Redundant Pathways for Negative Feedback Regulation of Bile Acid Production
Wang, L., Lee, Y., Bundman, D. S., Han, Y., Thevananther, S., Kim, C.-S., Chua, S. S., Wei, P. Y., Heyman, R. A., Karin, M., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00187-9 · Cited by 475 · see citing works
Self-citationActivation of c-Jun N-terminal kinase in bacterial lipopolysaccharide-stimulated macrophages.
Hambleton, J., Weinstein, S. L., Lem, L., & DeFranco, A. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.7.2774 · Cited by 471 · see citing works
The JIP Group of Mitogen-Activated Protein Kinase Scaffold Proteins
Yasuda, J., Whitmarsh, A. J., Cavanagh, J., Sharma, M., & Davis, R. J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.10.7245 · Cited by 458 · see citing works
Self-citationBaud, V., Liu, Z.-G., Bennett, B. L., Suzuki, N., Xia, Y., & Karin, M. (1999) · Genes & Development · doi:10.1101/gad.13.10.1297 · Cited by 464 · see citing works
Self-citationRole of p38 and JNK Mitogen-Activated Protein Kinases in the Activation of Ternary Complex Factors
Whitmarsh, A. J., Yang, S., Su, M. S. S., Sharrocks, A. D., & Davis, R. J. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.5.2360 · Cited by 454 · see citing works
Self-citationDocking domains and substrate-specificity determination for MAP kinases
Sharrocks, A. D., Yang, S.-H., & Galanis, A. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01627-3 · Cited by 442 · see citing works
Jacobs, D., Glossip, D., Xing, H., Muslin, A. J., & Kornfeld, K. (1999) · Genes & Development · doi:10.1101/gad.13.2.163 · Cited by 439 · see citing works
Big Mitogen-activated Protein Kinase 1 (BMK1) Is a Redox-sensitive Kinase
Abe, J., Kusuhara, M., Ulevitch, R. J., Berk, B. C., & Lee, J.-D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.28.16586 · Cited by 441 · see citing works
Structural basis of inhibitor selectivity in MAP kinases
Wang, Z., Canagarajah, B. J., Boehm, J. C., Kassisà, S., Cobb, M. H., Young, P. R., Abdel‐Meguid, S. S., Adams, J. L., & Goldsmith, E. J. (1998) · Structure · doi:10.1016/s0969-2126(98)00113-0 · Cited by 426 · see citing works
The tumor promoter arsenite stimulates AP‐1 activity by inhibiting a JNK phosphatase.
Cavigelli, M., Li, W. W., Lin, A., Su, B., Yoshioka, K., & Karin, M. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01017.x · Cited by 415 · see citing works
Self-citationFrom JNK to Pay Dirt: Jun Kinases, their Biochemistry, Physiology and Clinical Importance
Karin, M., & Gallagher, E. D. (2005) · IUBMB Life · doi:10.1080/15216540500097111 · Cited by 414 · see citing works
Self-citationRole of Curcumin in Cancer Therapy
Shishodia, S., Chaturvedi, M. M., & Aggarwal, B. B. (2007) · Current Problems in Cancer · doi:10.1016/j.currproblcancer.2007.04.001 · Cited by 413 · see citing works
A JNK signal transduction pathway that mediates morphogenesis and an immune response in Drosophila.Preprint
Sluss, H. K., Han, Z., Barrett, T., Davis, R. J., & Ip, Y. T. (1996) · Genes & Development · doi:10.1101/gad.10.21.2745 · Cited by 412 · see citing works
Self-citationDistinct 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
Self-citationJNK2 and IKKβ Are Required for Activating the Innate Response to Viral Infection
Chu, W., Ostertag, D. G., Li, Z.-W., Chang, L., Chen, Y., Hu, Y., Williams, B. R. G., Perrault, J., & Karin, M. (1999) · Immunity · doi:10.1016/s1074-7613(00)80146-6 · Cited by 389 · see citing works
Self-citationAP-1: One Switch for Many Signals
Wisdom, R. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4685 · Cited by 385 · see citing works
Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH 2 -terminal kinase
Tournier, C., Whitmarsh, A. J., Cavanagh, J., Barrett, T., & Davis, R. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7337 · Cited by 377 · see citing works
Self-citationChang, L., Jones, Y., Ellisman, M. H., Goldstein, L. S. B., & Karin, M. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00094-7 · Cited by 375 · see citing works
Self-citationSeeger, M., Kraft, R., Ferrell, K., Bech‐Otschir, D., Dumdey, R., Schade, R., Gordon, C., Naumann, M., & Dubiel, W. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.6.469 · Cited by 365 · see citing works
Tissue-specific Pattern of Stress Kinase Activation in Ischemic/Reperfused Heart and Kidney
Yin, T., Sandhu, G., Wolfgang, C. D., Burrier, A. C., Webb, R. L., Rigel, D. F., Hai, T., & Whelan, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.32.19943 · Cited by 364 · see citing works
Glutathione in liver diseases and hepatotoxicity
Yuan, L., & Kaplowitz, N. (2008) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.08.003 · Cited by 359 · see citing works
Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2
Sabapathy, K., Jochum, W., Hochedlinger, K., Chang, L., Karin, M., & Wagner, E. F. (1999) · Mechanisms of Development · doi:10.1016/s0925-4773(99)00213-0 · Cited by 359 · see citing works
Self-citationThree distinct signalling responses by murine fibroblasts to genotoxic stress
Liu, Z.-G., Rajasekaran, B., Lea-Chou, E., Wood, L. D., Chen, Y., Karin, M., & Wang, J. Y. J. (1996) · Nature · doi:10.1038/384273a0 · Cited by 355 · see citing works
Self-citationDifferent Toll-like receptor agonists induce distinct macrophage responses
Jones, B. W., Means, T. K., Heldwein, K. A., Keen, M. A., Hill, P. J., Belisle, J. T., & Fenton, M. J. (2001) · Journal of Leukocyte Biology · doi:10.1189/jlb.69.6.1036 · Cited by 353 · see citing works
Discovery of Potent and Selective Covalent Inhibitors of JNK
Zhang, T., Iñesta-Vaquera, F., Niepel, M., Zhang, J., Ficarro, S. B., Machleidt, T., Xie, T., Marto, J. A., Kim, N., Sim, T., et al. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2011.11.010 · Cited by 348 · see citing works
Wang, T., Wang, H.-S., Ichijo, H., Giannakakou, P., Foster, J. S., Fojo, T., & Wimalasena, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.9.4928 · Cited by 353 · see citing works
Stabilization of Interleukin-2 mRNA by the c-Jun NH 2 -Terminal Kinase Pathway
Chen, C., Gatto–Konczak, F. D., Wu, Z., & Karin, M. (1998) · Science · doi:10.1126/science.280.5371.1945 · Cited by 349 · see citing works
Self-citationATF-2 Is a Common Nuclear Target of Smad and TAK1 Pathways in Transforming Growth Factor-β Signaling
Sano, Y., Harada, J., Tashiro, S., Goto‐Mandeville, R., Maekawa, T., & Ishii, S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.13.8949 · Cited by 345 · see citing works
Signalling specificity of Ser/Thr protein kinases through docking-site-mediated interactions
BIONDI, R. M., & NEBREDA, A. R. (2003) · Biochemical Journal · doi:10.1042/bj20021641 · Cited by 334 · see citing works
Deletion of the loop region of Bcl-2 completely blocks paclitaxel-induced apoptosis
Srivastava, R. K., Mi, Q., Hardwick, J. M., & Longo, D. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3775 · Cited by 335 · 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
The regulation of AP-1 activity by mitogen-activated protein kinases
Karin, M., & Marshall, C. J. (1996) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.1996.0008 · Cited by 332 · see citing works
Self-citationHerdegen, T., Claret, F.-X., Kallunki, T., Martín-Villalba, A., Winter, C., Hunter, T., & Karin, M. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-14-05124.1998 · Cited by 327 · see citing works
Self-citationMitogen-Activated Protein Kinase Cascades as Regulators of Stress Responses
Karin, M. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb08987.x · Cited by 327 · see citing works
Self-citationMolecular basis of MAP kinase regulation
Peti, W., & Page, R. (2013) · Protein Science · doi:10.1002/pro.2374 · Cited by 302 · see citing works
“binds a conserved 13–16 amino acid sequence known as the D- or KIM-motif (kinase interaction motif).(19) The KIM-motif has a well-established consensus”
Backgroundc-Jun N-terminal kinase (JNK) signaling: Recent advances and challenges
Bogoyevitch, M. A., Ngoei, K. R. W., Zhao, T. T., Yeap, Y. Y. C., & Ng, D. C. H. (2009) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.11.002 · Cited by 326 · see citing works
Riesgo‐Escovar, J. R., Jenni, M., Fritz, A. L., & Hafen, E. (1996) · Genes & Development · doi:10.1101/gad.10.21.2759 · Cited by 313 · see citing works
Chang, C.-I., Xu, B.-E., Akella, R., Cobb, M. H., & Goldsmith, E. J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00525-7 · Cited by 302 · see citing works
Chen, B. P. C., Wolfgang, C. D., & Hai, T. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.3.1157 · Cited by 304 · see citing works
Hui, L., Zatloukal, K., Scheuch, H., Stępniak-Konieczna, E., & Wagner, E. F. (2008) · Journal of Clinical Investigation · doi:10.1172/jci37156 · Cited by 308 · see citing works
Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38
Harper, S. J., & LoGrasso, P. V. (2001) · Cellular Signalling · doi:10.1016/s0898-6568(01)00148-6 · Cited by 304 · see citing works
- Authors
- Kallunki, T., Su, B., Tsigelny, I., Sluss, H. K., Dérijard, B., Moore, G., Davis, R., & Karin, M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1994-12-15
- Volume
- 8
- Issue
- 24
- Pages
- 2996-3007
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W1972145919
- Cited by
- 642
- References
- 34
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 8 · 2017: 8 · 2016: 7 · 2015: 6 · 2014: 15 · 2013: 15 · 2012: 21
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy
- National Institutes of Health
- 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 › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- JNK2, c-Jun, c-Jun N-terminal kinase, mitogen-activated protein kinase, substrate specificity, protein-protein interaction, c-Jun phosphorylation, docking site, catalytic pocket, JNK1, transcriptional activation, gene cloning
- MeSH terms
- Amino Acid Sequence, Binding Sites, Cell Line, Cloning, Molecular, Humans, Kinetics, Models, Molecular, Molecular Sequence Data, Molecular Weight, Protein Kinases, Transfection, Tumor Cells, Cultured, Gene Expression, Proto-Oncogene Proteins c-jun, Conserved Sequence, Sequence Homology, Amino Acid, Protein Structure, Secondary, Calcium-Calmodulin-Dependent Protein Kinases, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 9
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
