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. 1997 May;17(5):2360–2371. doi: 10.1128/mcb.17.5.2360

Role of p38 and JNK mitogen-activated protein kinases in the activation of ternary complex factors.

A J Whitmarsh 1, S H Yang 1, M S Su 1, A D Sharrocks 1, R J Davis 1
PMCID: PMC232085  PMID: 9111305

Abstract

The transcription factors Elk-1 and SAP-1 bind together with serum response factor to the serum response element present in the c-fos promoter and mediate increased gene expression. The ERK, JNK, and p38 groups of mitogen-activated protein (MAP) kinases phosphorylate and activate Elk-1 in response to a variety of extracellular stimuli. In contrast, SAP-1 is activated by ERK and p38 MAP kinases but not by JNK. The proinflammatory cytokine interleukin-1 (IL-1) activates JNK and p38 MAP kinases and induces the transcriptional activity of Elk-1 and SAP-1. These effects of IL-1 appear to be mediated by Rho family GTPases. To examine the relative roles of the JNK and p38 MAP kinase pathways, we examined the effects of IL-1 on CHO and NIH 3T3 cells. Studies of NIH 3T3 cells demonstrated that both the JNK and p38 MAP kinases are required for IL-1-stimulated Elk-1 transcriptional activity, while only p38 MAP kinase contributes to IL-1-induced activation of SAP-1. In contrast, studies of CHO cells demonstrated that JNK (but not the p38 MAP kinase) is required for IL-1-stimulated Elk-1-dependent gene expression and that neither JNK nor p38 MAP kinase is required for IL-1 signaling to SAP-1. We conclude that (i) distinct MAP kinase signal transduction pathways mediate IL-1 signaling to ternary complex transcription factors (TCFs) in different cell types and (ii) individual TCFs show different responses to the JNK and p38 signaling pathways. The differential utilization of TCF proteins and MAP kinase signaling pathways represents a potential mechanism for the determination of cell-type-specific responses to extracellular stimuli.

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Selected References

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  1. Abe J., Kusuhara M., Ulevitch R. J., Berk B. C., Lee J. D. Big mitogen-activated protein kinase 1 (BMK1) is a redox-sensitive kinase. J Biol Chem. 1996 Jul 12;271(28):16586–16590. doi: 10.1074/jbc.271.28.16586. [DOI] [PubMed] [Google Scholar]
  2. Bagrodia S., Dérijard B., Davis R. J., Cerione R. A. Cdc42 and PAK-mediated signaling leads to Jun kinase and p38 mitogen-activated protein kinase activation. J Biol Chem. 1995 Nov 24;270(47):27995–27998. doi: 10.1074/jbc.270.47.27995. [DOI] [PubMed] [Google Scholar]
  3. Bagrodia S., Taylor S. J., Creasy C. L., Chernoff J., Cerione R. A. Identification of a mouse p21Cdc42/Rac activated kinase. J Biol Chem. 1995 Sep 29;270(39):22731–22737. doi: 10.1074/jbc.270.39.22731. [DOI] [PubMed] [Google Scholar]
  4. Blank J. L., Gerwins P., Elliott E. M., Sather S., Johnson G. L. Molecular cloning of mitogen-activated protein/ERK kinase kinases (MEKK) 2 and 3. Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase. J Biol Chem. 1996 Mar 8;271(10):5361–5368. doi: 10.1074/jbc.271.10.5361. [DOI] [PubMed] [Google Scholar]
  5. Brown J. L., Stowers L., Baer M., Trejo J., Coughlin S., Chant J. Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway. Curr Biol. 1996 May 1;6(5):598–605. doi: 10.1016/s0960-9822(02)00546-8. [DOI] [PubMed] [Google Scholar]
  6. Burbelo P. D., Drechsel D., Hall A. A conserved binding motif defines numerous candidate target proteins for both Cdc42 and Rac GTPases. J Biol Chem. 1995 Dec 8;270(49):29071–29074. doi: 10.1074/jbc.270.49.29071. [DOI] [PubMed] [Google Scholar]
  7. Cahill M. A., Janknecht R., Nordheim A. Signalling pathways: jack of all cascades. Curr Biol. 1996 Jan 1;6(1):16–19. doi: 10.1016/s0960-9822(02)00410-4. [DOI] [PubMed] [Google Scholar]
  8. Cano E., Hazzalin C. A., Kardalinou E., Buckle R. S., Mahadevan L. C. Neither ERK nor JNK/SAPK MAP kinase subtypes are essential for histone H3/HMG-14 phosphorylation or c-fos and c-jun induction. J Cell Sci. 1995 Nov;108(Pt 11):3599–3609. doi: 10.1242/jcs.108.11.3599. [DOI] [PubMed] [Google Scholar]
  9. Cavigelli M., Dolfi F., Claret F. X., Karin M. Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation. EMBO J. 1995 Dec 1;14(23):5957–5964. doi: 10.1002/j.1460-2075.1995.tb00284.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Coso O. A., Chiariello M., Yu J. C., Teramoto H., Crespo P., Xu N., Miki T., Gutkind J. S. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell. 1995 Jun 30;81(7):1137–1146. doi: 10.1016/s0092-8674(05)80018-2. [DOI] [PubMed] [Google Scholar]
  11. Cuenda A., Rouse J., Doza Y. N., Meier R., Cohen P., Gallagher T. F., Young P. R., Lee J. C. SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett. 1995 May 8;364(2):229–233. doi: 10.1016/0014-5793(95)00357-f. [DOI] [PubMed] [Google Scholar]
  12. Dalton S., Treisman R. Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell. 1992 Feb 7;68(3):597–612. doi: 10.1016/0092-8674(92)90194-h. [DOI] [PubMed] [Google Scholar]
  13. Davis R. J. MAPKs: new JNK expands the group. Trends Biochem Sci. 1994 Nov;19(11):470–473. doi: 10.1016/0968-0004(94)90132-5. [DOI] [PubMed] [Google Scholar]
  14. Davis R. J. The mitogen-activated protein kinase signal transduction pathway. J Biol Chem. 1993 Jul 15;268(20):14553–14556. [PubMed] [Google Scholar]
  15. Dérijard B., Hibi M., Wu I. H., Barrett T., Su B., Deng T., Karin M., Davis R. J. JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell. 1994 Mar 25;76(6):1025–1037. doi: 10.1016/0092-8674(94)90380-8. [DOI] [PubMed] [Google Scholar]
  16. Dérijard B., Raingeaud J., Barrett T., Wu I. H., Han J., Ulevitch R. J., Davis R. J. Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. Science. 1995 Feb 3;267(5198):682–685. doi: 10.1126/science.7839144. [DOI] [PubMed] [Google Scholar]
  17. Gille H., Kortenjann M., Thomae O., Moomaw C., Slaughter C., Cobb M. H., Shaw P. E. ERK phosphorylation potentiates Elk-1-mediated ternary complex formation and transactivation. EMBO J. 1995 Mar 1;14(5):951–962. doi: 10.1002/j.1460-2075.1995.tb07076.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gille H., Sharrocks A. D., Shaw P. E. Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at c-fos promoter. Nature. 1992 Jul 30;358(6385):414–417. doi: 10.1038/358414a0. [DOI] [PubMed] [Google Scholar]
  19. Gille H., Strahl T., Shaw P. E. Activation of ternary complex factor Elk-1 by stress-activated protein kinases. Curr Biol. 1995 Oct 1;5(10):1191–1200. doi: 10.1016/s0960-9822(95)00235-1. [DOI] [PubMed] [Google Scholar]
  20. Giovane A., Pintzas A., Maira S. M., Sobieszczuk P., Wasylyk B. Net, a new ets transcription factor that is activated by Ras. Genes Dev. 1994 Jul 1;8(13):1502–1513. doi: 10.1101/gad.8.13.1502. [DOI] [PubMed] [Google Scholar]
  21. Gupta S., Barrett T., Whitmarsh A. J., Cavanagh J., Sluss H. K., Dérijard B., Davis R. J. Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J. 1996 Jun 3;15(11):2760–2770. [PMC free article] [PubMed] [Google Scholar]
  22. Gupta S., Campbell D., Dérijard B., Davis R. J. Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science. 1995 Jan 20;267(5196):389–393. doi: 10.1126/science.7824938. [DOI] [PubMed] [Google Scholar]
  23. Han J., Lee J. D., Bibbs L., Ulevitch R. J. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science. 1994 Aug 5;265(5173):808–811. doi: 10.1126/science.7914033. [DOI] [PubMed] [Google Scholar]
  24. Han J., Lee J. D., Jiang Y., Li Z., Feng L., Ulevitch R. J. Characterization of the structure and function of a novel MAP kinase kinase (MKK6). J Biol Chem. 1996 Feb 9;271(6):2886–2891. doi: 10.1074/jbc.271.6.2886. [DOI] [PubMed] [Google Scholar]
  25. Hibi M., Lin A., Smeal T., Minden A., Karin M. Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 1993 Nov;7(11):2135–2148. doi: 10.1101/gad.7.11.2135. [DOI] [PubMed] [Google Scholar]
  26. Hill C. S., Wynne J., Treisman R. The Rho family GTPases RhoA, Rac1, and CDC42Hs regulate transcriptional activation by SRF. Cell. 1995 Jun 30;81(7):1159–1170. doi: 10.1016/s0092-8674(05)80020-0. [DOI] [PubMed] [Google Scholar]
  27. Hipskind R. A., Rao V. N., Mueller C. G., Reddy E. S., Nordheim A. Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF. Nature. 1991 Dec 19;354(6354):531–534. doi: 10.1038/354531a0. [DOI] [PubMed] [Google Scholar]
  28. Hirai S., Izawa M., Osada S., Spyrou G., Ohno S. Activation of the JNK pathway by distantly related protein kinases, MEKK and MUK. Oncogene. 1996 Feb 1;12(3):641–650. [PubMed] [Google Scholar]
  29. Janknecht R., Ernst W. H., Nordheim A. SAP1a is a nuclear target of signaling cascades involving ERKs. Oncogene. 1995 Mar 16;10(6):1209–1216. [PubMed] [Google Scholar]
  30. Janknecht R., Ernst W. H., Pingoud V., Nordheim A. Activation of ternary complex factor Elk-1 by MAP kinases. EMBO J. 1993 Dec 15;12(13):5097–5104. doi: 10.1002/j.1460-2075.1993.tb06204.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Janknecht R., Nordheim A. Elk-1 protein domains required for direct and SRF-assisted DNA-binding. Nucleic Acids Res. 1992 Jul 11;20(13):3317–3324. doi: 10.1093/nar/20.13.3317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Janknecht R., Nordheim A. Gene regulation by Ets proteins. Biochim Biophys Acta. 1993 Dec 23;1155(3):346–356. doi: 10.1016/0304-419x(93)90014-4. [DOI] [PubMed] [Google Scholar]
  33. Kallunki T., Su B., Tsigelny I., Sluss H. K., Dérijard B., Moore G., Davis R., Karin M. JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation. Genes Dev. 1994 Dec 15;8(24):2996–3007. doi: 10.1101/gad.8.24.2996. [DOI] [PubMed] [Google Scholar]
  34. Khosravi-Far R., Solski P. A., Clark G. J., Kinch M. S., Der C. J. Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation. Mol Cell Biol. 1995 Nov;15(11):6443–6453. doi: 10.1128/mcb.15.11.6443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Khosravi-Far R., White M. A., Westwick J. K., Solski P. A., Chrzanowska-Wodnicka M., Van Aelst L., Wigler M. H., Der C. J. Oncogenic Ras activation of Raf/mitogen-activated protein kinase-independent pathways is sufficient to cause tumorigenic transformation. Mol Cell Biol. 1996 Jul;16(7):3923–3933. doi: 10.1128/mcb.16.7.3923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Knaus U. G., Morris S., Dong H. J., Chernoff J., Bokoch G. M. Regulation of human leukocyte p21-activated kinases through G protein--coupled receptors. Science. 1995 Jul 14;269(5221):221–223. doi: 10.1126/science.7618083. [DOI] [PubMed] [Google Scholar]
  37. Kyriakis J. M., Banerjee P., Nikolakaki E., Dai T., Rubie E. A., Ahmad M. F., Avruch J., Woodgett J. R. The stress-activated protein kinase subfamily of c-Jun kinases. Nature. 1994 May 12;369(6476):156–160. doi: 10.1038/369156a0. [DOI] [PubMed] [Google Scholar]
  38. Lee J. C., Laydon J. T., McDonnell P. C., Gallagher T. F., Kumar S., Green D., McNulty D., Blumenthal M. J., Heys J. R., Landvatter S. W. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature. 1994 Dec 22;372(6508):739–746. doi: 10.1038/372739a0. [DOI] [PubMed] [Google Scholar]
  39. Lee J. D., Ulevitch R. J., Han J. Primary structure of BMK1: a new mammalian map kinase. Biochem Biophys Res Commun. 1995 Aug 15;213(2):715–724. doi: 10.1006/bbrc.1995.2189. [DOI] [PubMed] [Google Scholar]
  40. Lin A., Minden A., Martinetto H., Claret F. X., Lange-Carter C., Mercurio F., Johnson G. L., Karin M. Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. Science. 1995 Apr 14;268(5208):286–290. doi: 10.1126/science.7716521. [DOI] [PubMed] [Google Scholar]
  41. Liu Y., Gorospe M., Yang C., Holbrook N. J. Role of mitogen-activated protein kinase phosphatase during the cellular response to genotoxic stress. Inhibition of c-Jun N-terminal kinase activity and AP-1-dependent gene activation. J Biol Chem. 1995 Apr 14;270(15):8377–8380. doi: 10.1074/jbc.270.15.8377. [DOI] [PubMed] [Google Scholar]
  42. Livingstone C., Patel G., Jones N. ATF-2 contains a phosphorylation-dependent transcriptional activation domain. EMBO J. 1995 Apr 18;14(8):1785–1797. doi: 10.1002/j.1460-2075.1995.tb07167.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Lopez M., Oettgen P., Akbarali Y., Dendorfer U., Libermann T. A. ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development. Mol Cell Biol. 1994 May;14(5):3292–3309. doi: 10.1128/mcb.14.5.3292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Manser E., Leung T., Salihuddin H., Zhao Z. S., Lim L. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature. 1994 Jan 6;367(6458):40–46. doi: 10.1038/367040a0. [DOI] [PubMed] [Google Scholar]
  45. Mansour S. J., Matten W. T., Hermann A. S., Candia J. M., Rong S., Fukasawa K., Vande Woude G. F., Ahn N. G. Transformation of mammalian cells by constitutively active MAP kinase kinase. Science. 1994 Aug 12;265(5174):966–970. doi: 10.1126/science.8052857. [DOI] [PubMed] [Google Scholar]
  46. Marais R., Wynne J., Treisman R. The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain. Cell. 1993 Apr 23;73(2):381–393. doi: 10.1016/0092-8674(93)90237-k. [DOI] [PubMed] [Google Scholar]
  47. Martin G. A., Bollag G., McCormick F., Abo A. A novel serine kinase activated by rac1/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20. EMBO J. 1995 May 1;14(9):1970–1978. doi: 10.1002/j.1460-2075.1995.tb07189.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Minden A., Lin A., Claret F. X., Abo A., Karin M. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell. 1995 Jun 30;81(7):1147–1157. doi: 10.1016/s0092-8674(05)80019-4. [DOI] [PubMed] [Google Scholar]
  49. Minden A., Lin A., McMahon M., Lange-Carter C., Dérijard B., Davis R. J., Johnson G. L., Karin M. Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science. 1994 Dec 9;266(5191):1719–1723. doi: 10.1126/science.7992057. [DOI] [PubMed] [Google Scholar]
  50. Miranti C. K., Ginty D. D., Huang G., Chatila T., Greenberg M. E. Calcium activates serum response factor-dependent transcription by a Ras- and Elk-1-independent mechanism that involves a Ca2+/calmodulin-dependent kinase. Mol Cell Biol. 1995 Jul;15(7):3672–3684. doi: 10.1128/mcb.15.7.3672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Moriguchi T., Kuroyanagi N., Yamaguchi K., Gotoh Y., Irie K., Kano T., Shirakabe K., Muro Y., Shibuya H., Matsumoto K. A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3. J Biol Chem. 1996 Jun 7;271(23):13675–13679. doi: 10.1074/jbc.271.23.13675. [DOI] [PubMed] [Google Scholar]
  52. Olson M. F., Ashworth A., Hall A. An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through G1. Science. 1995 Sep 1;269(5228):1270–1272. doi: 10.1126/science.7652575. [DOI] [PubMed] [Google Scholar]
  53. Price M. A., Rogers A. E., Treisman R. Comparative analysis of the ternary complex factors Elk-1, SAP-1a and SAP-2 (ERP/NET). EMBO J. 1995 Jun 1;14(11):2589–2601. doi: 10.1002/j.1460-2075.1995.tb07257.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Qiu R. G., Chen J., Kirn D., McCormick F., Symons M. An essential role for Rac in Ras transformation. Nature. 1995 Mar 30;374(6521):457–459. doi: 10.1038/374457a0. [DOI] [PubMed] [Google Scholar]
  55. Qiu R. G., Chen J., McCormick F., Symons M. A role for Rho in Ras transformation. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11781–11785. doi: 10.1073/pnas.92.25.11781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Raingeaud J., Gupta S., Rogers J. S., Dickens M., Han J., Ulevitch R. J., Davis R. J. Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem. 1995 Mar 31;270(13):7420–7426. doi: 10.1074/jbc.270.13.7420. [DOI] [PubMed] [Google Scholar]
  57. Raingeaud J., Whitmarsh A. J., Barrett T., Dérijard B., Davis R. J. MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway. Mol Cell Biol. 1996 Mar;16(3):1247–1255. doi: 10.1128/mcb.16.3.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Rana A., Gallo K., Godowski P., Hirai S., Ohno S., Zon L., Kyriakis J. M., Avruch J. The mixed lineage kinase SPRK phosphorylates and activates the stress-activated protein kinase activator, SEK-1. J Biol Chem. 1996 Aug 9;271(32):19025–19028. doi: 10.1074/jbc.271.32.19025. [DOI] [PubMed] [Google Scholar]
  59. Ridley A. J. Rho-related proteins: actin cytoskeleton and cell cycle. Curr Opin Genet Dev. 1995 Feb;5(1):24–30. doi: 10.1016/s0959-437x(95)90049-7. [DOI] [PubMed] [Google Scholar]
  60. Russell M., Lange-Carter C. A., Johnson G. L. Direct interaction between Ras and the kinase domain of mitogen-activated protein kinase kinase kinase (MEKK1). J Biol Chem. 1995 May 19;270(20):11757–11760. doi: 10.1074/jbc.270.20.11757. [DOI] [PubMed] [Google Scholar]
  61. Sadowski I., Ptashne M. A vector for expressing GAL4(1-147) fusions in mammalian cells. Nucleic Acids Res. 1989 Sep 25;17(18):7539–7539. doi: 10.1093/nar/17.18.7539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Salmeron A., Ahmad T. B., Carlile G. W., Pappin D., Narsimhan R. P., Ley S. C. Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase. EMBO J. 1996 Feb 15;15(4):817–826. [PMC free article] [PubMed] [Google Scholar]
  63. Seth A., Gonzalez F. A., Gupta S., Raden D. L., Davis R. J. Signal transduction within the nucleus by mitogen-activated protein kinase. J Biol Chem. 1992 Dec 5;267(34):24796–24804. [PubMed] [Google Scholar]
  64. Sharrocks A. D. ERK2/p42 MAP kinase stimulates both autonomous and SRF-dependent DNA binding by Elk-1. FEBS Lett. 1995 Jul 10;368(1):77–80. doi: 10.1016/0014-5793(95)00604-8. [DOI] [PubMed] [Google Scholar]
  65. Shibuya H., Yamaguchi K., Shirakabe K., Tonegawa A., Gotoh Y., Ueno N., Irie K., Nishida E., Matsumoto K. TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction. Science. 1996 May 24;272(5265):1179–1182. doi: 10.1126/science.272.5265.1179. [DOI] [PubMed] [Google Scholar]
  66. Shore P., Sharrocks A. D. The ETS-domain transcription factors Elk-1 and SAP-1 exhibit differential DNA binding specificities. Nucleic Acids Res. 1995 Nov 25;23(22):4698–4706. doi: 10.1093/nar/23.22.4698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Shore P., Sharrocks A. D. The transcription factors Elk-1 and serum response factor interact by direct protein-protein contacts mediated by a short region of Elk-1. Mol Cell Biol. 1994 May;14(5):3283–3291. doi: 10.1128/mcb.14.5.3283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Shore P., Whitmarsh A. J., Bhaskaran R., Davis R. J., Waltho J. P., Sharrocks A. D. Determinants of DNA-binding specificity of ETS-domain transcription factors. Mol Cell Biol. 1996 Jul;16(7):3338–3349. doi: 10.1128/mcb.16.7.3338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Sluss H. K., Barrett T., Dérijard B., Davis R. J. Signal transduction by tumor necrosis factor mediated by JNK protein kinases. Mol Cell Biol. 1994 Dec;14(12):8376–8384. doi: 10.1128/mcb.14.12.8376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Stein B., Brady H., Yang M. X., Young D. B., Barbosa M. S. Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade. J Biol Chem. 1996 May 10;271(19):11427–11433. doi: 10.1074/jbc.271.19.11427. [DOI] [PubMed] [Google Scholar]
  71. Sun H., Charles C. H., Lau L. F., Tonks N. K. MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell. 1993 Nov 5;75(3):487–493. doi: 10.1016/0092-8674(93)90383-2. [DOI] [PubMed] [Google Scholar]
  72. Sánchez I., Hughes R. T., Mayer B. J., Yee K., Woodgett J. R., Avruch J., Kyriakis J. M., Zon L. I. Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. Nature. 1994 Dec 22;372(6508):794–798. doi: 10.1038/372794a0. [DOI] [PubMed] [Google Scholar]
  73. Teramoto H., Coso O. A., Miyata H., Igishi T., Miki T., Gutkind J. S. Signaling from the small GTP-binding proteins Rac1 and Cdc42 to the c-Jun N-terminal kinase/stress-activated protein kinase pathway. A role for mixed lineage kinase 3/protein-tyrosine kinase 1, a novel member of the mixed lineage kinase family. J Biol Chem. 1996 Nov 1;271(44):27225–27228. doi: 10.1074/jbc.271.44.27225. [DOI] [PubMed] [Google Scholar]
  74. Treisman R. Ternary complex factors: growth factor regulated transcriptional activators. Curr Opin Genet Dev. 1994 Feb;4(1):96–101. doi: 10.1016/0959-437x(94)90097-3. [DOI] [PubMed] [Google Scholar]
  75. Treisman R. The serum response element. Trends Biochem Sci. 1992 Oct;17(10):423–426. doi: 10.1016/0968-0004(92)90013-y. [DOI] [PubMed] [Google Scholar]
  76. Wang X. Z., Ron D. Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP Kinase. Science. 1996 May 31;272(5266):1347–1349. doi: 10.1126/science.272.5266.1347. [DOI] [PubMed] [Google Scholar]
  77. Wartmann M., Davis R. J. The native structure of the activated Raf protein kinase is a membrane-bound multi-subunit complex. J Biol Chem. 1994 Mar 4;269(9):6695–6701. [PubMed] [Google Scholar]
  78. Whitmarsh A. J., Davis R. J. Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med (Berl) 1996 Oct;74(10):589–607. doi: 10.1007/s001090050063. [DOI] [PubMed] [Google Scholar]
  79. Whitmarsh A. J., Shore P., Sharrocks A. D., Davis R. J. Integration of MAP kinase signal transduction pathways at the serum response element. Science. 1995 Jul 21;269(5222):403–407. doi: 10.1126/science.7618106. [DOI] [PubMed] [Google Scholar]
  80. Yamaguchi K., Shirakabe K., Shibuya H., Irie K., Oishi I., Ueno N., Taniguchi T., Nishida E., Matsumoto K. Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction. Science. 1995 Dec 22;270(5244):2008–2011. doi: 10.1126/science.270.5244.2008. [DOI] [PubMed] [Google Scholar]
  81. Yan M., Dai T., Deak J. C., Kyriakis J. M., Zon L. I., Woodgett J. R., Templeton D. J. Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1. Nature. 1994 Dec 22;372(6508):798–800. doi: 10.1038/372798a0. [DOI] [PubMed] [Google Scholar]
  82. Zhang S., Han J., Sells M. A., Chernoff J., Knaus U. G., Ulevitch R. J., Bokoch G. M. Rho family GTPases regulate p38 mitogen-activated protein kinase through the downstream mediator Pak1. J Biol Chem. 1995 Oct 13;270(41):23934–23936. doi: 10.1074/jbc.270.41.23934. [DOI] [PubMed] [Google Scholar]
  83. Zhou G., Bao Z. Q., Dixon J. E. Components of a new human protein kinase signal transduction pathway. J Biol Chem. 1995 May 26;270(21):12665–12669. doi: 10.1074/jbc.270.21.12665. [DOI] [PubMed] [Google Scholar]
  84. Zinck R., Cahill M. A., Kracht M., Sachsenmaier C., Hipskind R. A., Nordheim A. Protein synthesis inhibitors reveal differential regulation of mitogen-activated protein kinase and stress-activated protein kinase pathways that converge on Elk-1. Mol Cell Biol. 1995 Sep;15(9):4930–4938. doi: 10.1128/mcb.15.9.4930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. van Dam H., Wilhelm D., Herr I., Steffen A., Herrlich P., Angel P. ATF-2 is preferentially activated by stress-activated protein kinases to mediate c-jun induction in response to genotoxic agents. EMBO J. 1995 Apr 18;14(8):1798–1811. doi: 10.1002/j.1460-2075.1995.tb07168.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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