Mapk8

Summary

Gene Symbol: Mapk8
Description: mitogen-activated protein kinase 8
Alias: AI849689, JNK, JNK1, Prkm8, SAPK1, mitogen-activated protein kinase 8, JNK1 beta1 protein kinase, MAP kinase 8, MAPK 8, c-Jun N-terminal kinase 1, protein kinase mitogen-activated 8, stress-activated protein kinase JNK1
Species: mouse
Products:     Mapk8

Top Publications

  1. Jaeschke A, Karasarides M, Ventura J, Ehrhardt A, Zhang C, Flavell R, et al. JNK2 is a positive regulator of the cJun transcription factor. Mol Cell. 2006;23:899-911 pubmed
    ..Studies of Jnk1(-/-) and Jnk2(-/-) mice suggest that the JNK1 and JNK2 isoforms have opposite effects on cJun expression and ..
  2. Hübner A, Barrett T, Flavell R, Davis R. Multisite phosphorylation regulates Bim stability and apoptotic activity. Mol Cell. 2008;30:415-25 pubmed publisher
    ..Together, these data indicate that phosphorylation can regulate Bim by multiple mechanisms and that the phosphorylation of Bim on different sites can contribute to the sensitivity of cellular apoptotic responses. ..
  3. Wang Z, Cao N, Nantajit D, Fan M, Liu Y, Li J. Mitogen-activated protein kinase phosphatase-1 represses c-Jun NH2-terminal kinase-mediated apoptosis via NF-kappaB regulation. J Biol Chem. 2008;283:21011-23 pubmed publisher
    ..that MKP-1 was negatively bridging between NF-kappaB-mediated prosurvival pathway and c-Jun N-terminal kinase (JNK)-mediated proapoptotic response...
  4. Unger E, Piper M, Olofsson L, Xu A. Functional role of c-Jun-N-terminal kinase in feeding regulation. Endocrinology. 2010;151:671-82 pubmed publisher
    ..b>JNK1-deficient mice feed more upon central administration of glucocorticoids, and glucocorticoid receptor nuclear ..
  5. Abdelli S, Puyal J, Bielmann C, Buchillier V, Abderrahmani A, Clarke P, et al. JNK3 is abundant in insulin-secreting cells and protects against cytokine-induced apoptosis. Diabetologia. 2009;52:1871-80 pubmed publisher
    In insulin-secreting cells, activation of the c-Jun NH(2)-terminal kinase (JNK) pathway triggers apoptosis. Whereas JNK1 and JNK2 are ubiquitously produced, JNK3 has been described exclusively in neurons...
  6. Witczak C, Hirshman M, Jessen N, Fujii N, Seifert M, Brandauer J, et al. JNK1 deficiency does not enhance muscle glucose metabolism in lean mice. Biochem Biophys Res Commun. 2006;350:1063-8 pubmed
    Mice deficient in c-jun-NH(2)-terminal kinase 1 (JNK1) exhibit decreased fasting blood glucose and insulin levels, and protection against obesity-induced insulin resistance, suggesting increased glucose disposal into skeletal muscle...
  7. Zhang S, Lin Y, Kim Y, Hande M, Liu Z, Shen H. c-Jun N-terminal kinase mediates hydrogen peroxide-induced cell death via sustained poly(ADP-ribose) polymerase-1 activation. Cell Death Differ. 2007;14:1001-10 pubmed
    ..Our previous study has illustrated that c-Jun-N-terminal kinase 1 (JNK1) is the main executor in hydrogen peroxide (H(2)O(2))-induced nonapoptotic cell death...
  8. Papa S, Zazzeroni F, Fu Y, Bubici C, Alvarez K, Dean K, et al. Gadd45beta promotes hepatocyte survival during liver regeneration in mice by modulating JNK signaling. J Clin Invest. 2008;118:1911-23 pubmed publisher
    In the liver, the JNK cascade is induced downstream of TNF receptors (TNFRs) in response to inflammatory, microbial, and toxic challenges...
  9. Hui L, Zatloukal K, Scheuch H, Stepniak E, Wagner E. Proliferation of human HCC cells and chemically induced mouse liver cancers requires JNK1-dependent p21 downregulation. J Clin Invest. 2008;118:3943-53 pubmed publisher
    ..Here, we show that activation of JNK1 but not JNK2 was increased in human primary hepatocellular carcinomas (HCCs)...
  10. Das M, Sabio G, Jiang F, Rincon M, Flavell R, Davis R. Induction of hepatitis by JNK-mediated expression of TNF-alpha. Cell. 2009;136:249-60 pubmed publisher
    ..To test this hypothesis, we examined the phenotype of mice with compound disruption of the Jnk1 and Jnk2 genes...

Detail Information

Publications73

  1. Jaeschke A, Karasarides M, Ventura J, Ehrhardt A, Zhang C, Flavell R, et al. JNK2 is a positive regulator of the cJun transcription factor. Mol Cell. 2006;23:899-911 pubmed
    ..Studies of Jnk1(-/-) and Jnk2(-/-) mice suggest that the JNK1 and JNK2 isoforms have opposite effects on cJun expression and ..
  2. Hübner A, Barrett T, Flavell R, Davis R. Multisite phosphorylation regulates Bim stability and apoptotic activity. Mol Cell. 2008;30:415-25 pubmed publisher
    ..Together, these data indicate that phosphorylation can regulate Bim by multiple mechanisms and that the phosphorylation of Bim on different sites can contribute to the sensitivity of cellular apoptotic responses. ..
  3. Wang Z, Cao N, Nantajit D, Fan M, Liu Y, Li J. Mitogen-activated protein kinase phosphatase-1 represses c-Jun NH2-terminal kinase-mediated apoptosis via NF-kappaB regulation. J Biol Chem. 2008;283:21011-23 pubmed publisher
    ..that MKP-1 was negatively bridging between NF-kappaB-mediated prosurvival pathway and c-Jun N-terminal kinase (JNK)-mediated proapoptotic response...
  4. Unger E, Piper M, Olofsson L, Xu A. Functional role of c-Jun-N-terminal kinase in feeding regulation. Endocrinology. 2010;151:671-82 pubmed publisher
    ..b>JNK1-deficient mice feed more upon central administration of glucocorticoids, and glucocorticoid receptor nuclear ..
  5. Abdelli S, Puyal J, Bielmann C, Buchillier V, Abderrahmani A, Clarke P, et al. JNK3 is abundant in insulin-secreting cells and protects against cytokine-induced apoptosis. Diabetologia. 2009;52:1871-80 pubmed publisher
    In insulin-secreting cells, activation of the c-Jun NH(2)-terminal kinase (JNK) pathway triggers apoptosis. Whereas JNK1 and JNK2 are ubiquitously produced, JNK3 has been described exclusively in neurons...
  6. Witczak C, Hirshman M, Jessen N, Fujii N, Seifert M, Brandauer J, et al. JNK1 deficiency does not enhance muscle glucose metabolism in lean mice. Biochem Biophys Res Commun. 2006;350:1063-8 pubmed
    Mice deficient in c-jun-NH(2)-terminal kinase 1 (JNK1) exhibit decreased fasting blood glucose and insulin levels, and protection against obesity-induced insulin resistance, suggesting increased glucose disposal into skeletal muscle...
  7. Zhang S, Lin Y, Kim Y, Hande M, Liu Z, Shen H. c-Jun N-terminal kinase mediates hydrogen peroxide-induced cell death via sustained poly(ADP-ribose) polymerase-1 activation. Cell Death Differ. 2007;14:1001-10 pubmed
    ..Our previous study has illustrated that c-Jun-N-terminal kinase 1 (JNK1) is the main executor in hydrogen peroxide (H(2)O(2))-induced nonapoptotic cell death...
  8. Papa S, Zazzeroni F, Fu Y, Bubici C, Alvarez K, Dean K, et al. Gadd45beta promotes hepatocyte survival during liver regeneration in mice by modulating JNK signaling. J Clin Invest. 2008;118:1911-23 pubmed publisher
    In the liver, the JNK cascade is induced downstream of TNF receptors (TNFRs) in response to inflammatory, microbial, and toxic challenges...
  9. Hui L, Zatloukal K, Scheuch H, Stepniak E, Wagner E. Proliferation of human HCC cells and chemically induced mouse liver cancers requires JNK1-dependent p21 downregulation. J Clin Invest. 2008;118:3943-53 pubmed publisher
    ..Here, we show that activation of JNK1 but not JNK2 was increased in human primary hepatocellular carcinomas (HCCs)...
  10. Das M, Sabio G, Jiang F, Rincon M, Flavell R, Davis R. Induction of hepatitis by JNK-mediated expression of TNF-alpha. Cell. 2009;136:249-60 pubmed publisher
    ..To test this hypothesis, we examined the phenotype of mice with compound disruption of the Jnk1 and Jnk2 genes...
  11. Sabio G, Kennedy N, Cavanagh Kyros J, Jung D, Ko H, Ong H, et al. Role of muscle c-Jun NH2-terminal kinase 1 in obesity-induced insulin resistance. Mol Cell Biol. 2010;30:106-15 pubmed publisher
    ..by feeding of a high-fat diet (HFD) is associated with an increased activation of c-Jun NH(2)-terminal kinase 1 (JNK1)...
  12. Win S, Than T, Han D, Petrovic L, Kaplowitz N. c-Jun N-terminal kinase (JNK)-dependent acute liver injury from acetaminophen or tumor necrosis factor (TNF) requires mitochondrial Sab protein expression in mice. J Biol Chem. 2011;286:35071-8 pubmed publisher
    Sustained JNK activation plays a critical role in hepatotoxicity by acetaminophen or GalN/TNF-?...
  13. Solinas G, Vilcu C, Neels J, Bandyopadhyay G, Luo J, Naugler W, et al. JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity. Cell Metab. 2007;6:386-97 pubmed
    ..Activation of JNKs (mainly JNK1) in insulin target cells results in phosphorylation of insulin receptor substrates (IRSs) at serine and threonine ..
  14. Sclip A, Antoniou X, Colombo A, Camici G, Pozzi L, Cardinetti D, et al. c-Jun N-terminal kinase regulates soluble A? oligomers and cognitive impairment in AD mouse model. J Biol Chem. 2011;286:43871-80 pubmed publisher
    ..Here, we used the TgCRND8 AD mouse model to investigate the role of JNK in long term memory deficits...
  15. Morel C, Carlson S, White F, Davis R. Mcl-1 integrates the opposing actions of signaling pathways that mediate survival and apoptosis. Mol Cell Biol. 2009;29:3845-52 pubmed publisher
    ..Here we demonstrate that prior phosphorylation of Mcl-1 by the c-Jun N-terminal protein kinase (JNK) is essential for Mcl-1 phosphorylation by GSK3...
  16. Guma M, Ronacher L, Firestein G, Karin M, Corr M. JNK-1 deficiency limits macrophage-mediated antigen-induced arthritis. Arthritis Rheum. 2011;63:1603-12 pubmed publisher
    To elucidate the nonredundant roles of JNK-1 and JNK-2 in antigen-induced arthritis (AIA).
  17. Ciani L, Salinas P. c-Jun N-terminal kinase (JNK) cooperates with Gsk3beta to regulate Dishevelled-mediated microtubule stability. BMC Cell Biol. 2007;8:27 pubmed
    ..Here we show that the Wnt pathway also activates c-Jun N-terminal kinase (JNK) to regulate MT stabilization...
  18. Zhong S, Johnson D. The JNKs differentially regulate RNA polymerase III transcription by coordinately modulating the expression of all TFIIIB subunits. Proc Natl Acad Sci U S A. 2009;106:12682-7 pubmed publisher
    ..In both mouse and human cells, loss or reduction in JNK1 expression represses RNA pol III transcription...
  19. Mongan M, Wang J, Liu H, Fan Y, Jin C, Kao W, et al. Loss of MAP3K1 enhances proliferation and apoptosis during retinal development. Development. 2011;138:4001-12 pubmed publisher
    ..still occurs in knockout mice that have undergone tarsorrhaphy, but is absent in compound mutant Map3k1(+/?KD)Jnk1(-/-) and Map3k1(+/?KD)Jnk(+/-)Jnk2(+/-) mice that have EOB and reduced JNK signaling...
  20. Guma M, Kashiwakura J, Crain B, Kawakami Y, Beutler B, Firestein G, et al. JNK1 controls mast cell degranulation and IL-1{beta} production in inflammatory arthritis. Proc Natl Acad Sci U S A. 2010;107:22122-7 pubmed publisher
    ..The proinflammatory function of JNK1 requires bone marrow-derived cells, particularly mast cells...
  21. Solinas G, Naugler W, Galimi F, Lee M, Karin M. Saturated fatty acids inhibit induction of insulin gene transcription by JNK-mediated phosphorylation of insulin-receptor substrates. Proc Natl Acad Sci U S A. 2006;103:16454-9 pubmed
    JNKs are attractive targets for treatment of obesity and type-2 diabetes. A sustained increase in JNK activity was observed in dietary and genetic models of obesity in mice, whereas JNK deficiency prevented obesity-induced insulin ..
  22. Zakkar M, Chaudhury H, Sandvik G, Enesa K, Luong L, Cuhlmann S, et al. Increased endothelial mitogen-activated protein kinase phosphatase-1 expression suppresses proinflammatory activation at sites that are resistant to atherosclerosis. Circ Res. 2008;103:726-32 pubmed publisher
    ..vascular cell adhesion molecule [VCAM]-1) in endothelial cells (ECs) by activating p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein (MAP) kinases by phosphorylation...
  23. Sabio G, Cavanagh Kyros J, Barrett T, Jung D, Ko H, Ong H, et al. Role of the hypothalamic-pituitary-thyroid axis in metabolic regulation by JNK1. Genes Dev. 2010;24:256-64 pubmed publisher
    The cJun N-terminal kinase 1 (JNK1) is implicated in diet-induced obesity. Indeed, germline ablation of the murine Jnk1 gene prevents diet-induced obesity...
  24. Das M, Jiang F, Sluss H, Zhang C, Shokat K, Flavell R, et al. Suppression of p53-dependent senescence by the JNK signal transduction pathway. Proc Natl Acad Sci U S A. 2007;104:15759-64 pubmed
    ..using conditional and chemical genetic alleles of the ubiquitously expressed murine genes that encode the isoforms JNK1 and JNK2. Our analysis demonstrates that JNK is not essential for proliferation...
  25. Chambers J, LoGrasso P. Mitochondrial c-Jun N-terminal kinase (JNK) signaling initiates physiological changes resulting in amplification of reactive oxygen species generation. J Biol Chem. 2011;286:16052-62 pubmed publisher
    The JNK signaling cascade is critical for cellular responses to a variety of environmental and cellular stimuli...
  26. Denninger K, Rasmussen S, Larsen J, Orskov C, Seier Poulsen S, Sørensen P, et al. JNK1, but not JNK2, is required in two mechanistically distinct models of inflammatory arthritis. Am J Pathol. 2011;179:1884-93 pubmed publisher
    ..N-terminal kinases (JNKs) in inflammatory arthritis have been investigated; however, the roles of each isotype (ie, JNK1 and JNK2) in rheumatoid arthritis and conclusions about whether inhibition of one or both is necessary for ..
  27. Lin H, Tang C, Chen J, Chuang J, Huang S, Tan T, et al. Peptidoglycan induces interleukin-6 expression through the TLR2 receptor, JNK, c-Jun, and AP-1 pathways in microglia. J Cell Physiol. 2011;226:1573-82 pubmed publisher
    ..In contrast, PGN-induced IL-6 mRNA and protein up-regulation were attenuated by the SAPK/JNK (c-Jun N-terminal kinases) inhibitor SP600125...
  28. Li X, Weng H, Xu C, Reece E, Yang P. Oxidative stress-induced JNK1/2 activation triggers proapoptotic signaling and apoptosis that leads to diabetic embryopathy. Diabetes. 2012;61:2084-92 pubmed publisher
    ..We sought to determine whether 1) hyperglycemia-induced oxidative stress is responsible for the activation of JNK1/2 signaling, 2) JNK1 contributes to the teratogenicity of hyperglycemia, and 3) both JNK1 and JNK2 activation cause ..
  29. Cellurale C, Weston C, Reilly J, Garlick D, Jerry D, Sluss H, et al. Role of JNK in a Trp53-dependent mouse model of breast cancer. PLoS ONE. 2010;5:e12469 pubmed publisher
    ..To test the role of JNK, we examined the effect of ablation of the Jnk1 and Jnk2 genes in a Trp53-dependent model of breast cancer using BALB/c mice...
  30. VALLERIE S, Furuhashi M, Fucho R, Hotamisligil G. A predominant role for parenchymal c-Jun amino terminal kinase (JNK) in the regulation of systemic insulin sensitivity. PLoS ONE. 2008;3:e3151 pubmed publisher
    It has been established that c-Jun N-terminal kinase 1 (JNK1) is essential to the pathogenesis of insulin resistance and type 2 diabetes...
  31. Sabio G, Cavanagh Kyros J, Ko H, Jung D, Gray S, Jun J, et al. Prevention of steatosis by hepatic JNK1. Cell Metab. 2009;10:491-8 pubmed publisher
    ..The cJun NH(2)-terminal kinase 1 (JNK1) signaling pathway is implicated in the pathogenesis of hepatic steatosis and drugs that target JNK1 may be useful ..
  32. Sánchez Tilló E, Comalada M, Xaus J, Farrera C, Valledor A, Caelles C, et al. JNK1 Is required for the induction of Mkp1 expression in macrophages during proliferation and lipopolysaccharide-dependent activation. J Biol Chem. 2007;282:12566-73 pubmed
    ..The lack of Mkp1 induction caused by JNK inhibition prolonged ERK-1/2 and p38 phosphorylation. The two JNK genes, jnk1 and jnk2, are constitutively expressed in macrophages...
  33. Varona Santos J, Pileggi A, Molano R, Sanabria N, Ijaz A, Atsushi M, et al. c-Jun N-terminal kinase 1 is deleterious to the function and survival of murine pancreatic islets. Diabetologia. 2008;51:2271-80 pubmed publisher
    ..C57BL/6J (wild-type [WT]), Jnk1 (also known as Mapk8)(-/-) and Jnk2 (also known as Mapk9)(-/-) mice were used as donor/recipients in a syngeneic islet transplantation ..
  34. Alcorn J, van der Velden J, Brown A, McElhinney B, Irvin C, Janssen Heininger Y. c-Jun N-terminal kinase 1 is required for the development of pulmonary fibrosis. Am J Respir Cell Mol Biol. 2009;40:422-32 pubmed publisher
    ..The stress-activated protein kinase, c-Jun N-terminal kinase 1 (JNK1), is activated by a large variety of cellular stresses and environmental insults...
  35. Cellurale C, Girnius N, Jiang F, Cavanagh Kyros J, Lu S, Garlick D, et al. Role of JNK in mammary gland development and breast cancer. Cancer Res. 2012;72:472-81 pubmed publisher
    ..In this study, we employed a compound deletion of the murine Jnk1 and Jnk2 genes in the mammary gland to evaluate the requirement for these ubiquitously expressed genes in breast ..
  36. Takatori A, Geh E, Chen L, Zhang L, Meller J, Xia Y. Differential transmission of MEKK1 morphogenetic signals by JNK1 and JNK2. Development. 2008;135:23-32 pubmed
    b>JNK1 and JNK2 are two ubiquitously expressed isoforms that exert redundant roles in many physiological processes, but the extent of their relative contributions to these processes has not been well characterized...
  37. Svensson C, Inoue T, Hammaker D, Fukushima A, Papa S, Franzoso G, et al. Gadd45beta deficiency in rheumatoid arthritis: enhanced synovitis through JNK signaling. Arthritis Rheum. 2009;60:3229-40 pubmed publisher
    b>JNK-mediated cell signaling plays a critical role in matrix metalloproteinase (MMP) expression and joint destruction in rheumatoid arthritis (RA)...
  38. Velden J, Alcorn J, Guala A, Badura E, Janssen Heininger Y. c-Jun N-terminal kinase 1 promotes transforming growth factor-?1-induced epithelial-to-mesenchymal transition via control of linker phosphorylation and transcriptional activity of Smad3. Am J Respir Cell Mol Biol. 2011;44:571-81 pubmed publisher
    ..Because TGF-?1 signals via Smad complexes, the goal of the present study was to determine the impact of JNK1 on phosphorylation of Smad3 and Smad3-dependent transcriptional responses in lung epithelial cells...
  39. Sabio G, Das M, Mora A, Zhang Z, Jun J, Ko H, et al. A stress signaling pathway in adipose tissue regulates hepatic insulin resistance. Science. 2008;322:1539-43 pubmed publisher
    A high-fat diet causes activation of the regulatory protein c-Jun NH2-terminal kinase 1 (JNK1) and triggers development of insulin resistance. JNK1 is therefore a potential target for therapeutic treatment of metabolic syndrome...
  40. Chaudhury H, Zakkar M, Boyle J, Cuhlmann S, Van der Heiden K, Luong L, et al. c-Jun N-terminal kinase primes endothelial cells at atheroprone sites for apoptosis. Arterioscler Thromb Vasc Biol. 2010;30:546-53 pubmed publisher
    ..Analysis of aortae of wild-type, JNK1(-/-), and MKP-1(-/-) mice revealed that EC at an atherosusceptible site express proapoptotic proteins and are ..
  41. Belgardt B, Mauer J, Wunderlich F, Ernst M, Pal M, Spohn G, et al. Hypothalamic and pituitary c-Jun N-terminal kinase 1 signaling coordinately regulates glucose metabolism. Proc Natl Acad Sci U S A. 2010;107:6028-33 pubmed publisher
    ..To resolve the importance of JNK1 signaling in the hypothalamic/pituitary circuitry, we have generated mice with a conditional inactivation of JNK1 ..
  42. Ybot Gonzalez P, Savery D, Gerrelli D, Signore M, Mitchell C, Faux C, et al. Convergent extension, planar-cell-polarity signalling and initiation of mouse neural tube closure. Development. 2007;134:789-99 pubmed
    ..These findings identify a cell-autonomous defect of convergent extension, requiring PCP signalling via RhoA-Rho kinase, during the development of severe neural tube defects in the mouse. ..
  43. Yang R, Wilcox D, Haasch D, Jung P, Nguyen P, Voorbach M, et al. Liver-specific knockdown of JNK1 up-regulates proliferator-activated receptor gamma coactivator 1 beta and increases plasma triglyceride despite reduced glucose and insulin levels in diet-induced obese mice. J Biol Chem. 2007;282:22765-74 pubmed
    ..Genetic disruption of JNK1, but not JNK2, improves insulin sensitivity in diet-induced obese (DIO) mice...
  44. Alcorn J, Guala A, van der Velden J, McElhinney B, Irvin C, Davis R, et al. Jun N-terminal kinase 1 regulates epithelial-to-mesenchymal transition induced by TGF-beta1. J Cell Sci. 2008;121:1036-45 pubmed publisher
    ..Primary cultures of mouse tracheal epithelial cells (MTEC) from wild-type, JNK1-/- or JNK2-/- mice were comparatively evaluated for their ability to undergo EMT in response to TGF-beta1...
  45. Schwandner R, Yamaguchi K, Cao Z. Requirement of tumor necrosis factor receptor-associated factor (TRAF)6 in interleukin 17 signal transduction. J Exp Med. 2000;191:1233-40 pubmed
    ..that IL-17 activates the transcription factor nuclear factor (NF)-kappaB and c-Jun NH(2)-terminal kinase (JNK), the upstream signaling events are largely unknown...
  46. Dong C, Yang D, Wysk M, Whitmarsh A, Davis R, Flavell R. Defective T cell differentiation in the absence of Jnk1. Science. 1998;282:2092-5 pubmed
    ..JNK activity observed in wild-type activated TH cells was severely reduced in TH cells from Jnk1-/- mice...
  47. Matsuyama M, Mizusaki H, Shimono A, Mukai T, Okumura K, Abe K, et al. A novel isoform of Vinexin, Vinexin gamma, regulates Sox9 gene expression through activation of MAPK cascade in mouse fetal gonad. Genes Cells. 2005;10:421-34 pubmed
    ..Thus, Vinexin gamma seems to be implicated in regulation of Sox9 gene expression by modulating MAPK cascade in mouse fetal gonads. ..
  48. Kuan C, Yang D, Samanta Roy D, Davis R, Rakic P, Flavell R. The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron. 1999;22:667-76 pubmed
    ..Here, we address this issue using mutant mice lacking different members of the family (Jnk1, Jnk2, and Jnk3)...
  49. Morse D, Pischke S, Zhou Z, Davis R, Flavell R, Loop T, et al. Suppression of inflammatory cytokine production by carbon monoxide involves the JNK pathway and AP-1. J Biol Chem. 2003;278:36993-8 pubmed
    ..IL-1beta in response to LPS compared with control mice, and no effect of CO on these cytokine levels was seen in Jnk1 or Jnk2 genedeleted mice...
  50. Conze D, Krahl T, Kennedy N, Weiss L, Lumsden J, Hess P, et al. c-Jun NH(2)-terminal kinase (JNK)1 and JNK2 have distinct roles in CD8(+) T cell activation. J Exp Med. 2002;195:811-23 pubmed
    ..Here we examined the role of JNK1 and JNK2 in CD8(+) T cells...
  51. Tournier C, Whitmarsh A, Cavanagh J, Barrett T, Davis R. Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase. Proc Natl Acad Sci U S A. 1997;94:7337-42 pubmed
    The c-Jun NH2-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases is activated by phosphorylation on Thr and Tyr...
  52. David J, Sabapathy K, Hoffmann O, Idarraga M, Wagner E. JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and -independent mechanisms. J Cell Sci. 2002;115:4317-25 pubmed
    ..Using mice lacking JNK1 or JNK2, we demonstrate that JNK1, but not JNK2, is specifically activated by the osteoclast-differentiating factor ..
  53. Chang L, Jones Y, Ellisman M, Goldstein L, Karin M. JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins. Dev Cell. 2003;4:521-33 pubmed
    ..We found that a member of the c-Jun NH(2)-terminal protein kinase (JNK) subgroup of MAP kinases, JNK1, is involved in regulation of MT dynamics in neuronal cells...
  54. Chang L, Kamata H, Solinas G, Luo J, Maeda S, Venuprasad K, et al. The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnover. Cell. 2006;124:601-13 pubmed
    ..b>JNK1 or Itch deficiency or treatment with a JNK inhibitor renders mice resistant in three distinct models of TNFalpha-..
  55. Constant S, Dong C, Yang D, Wysk M, Davis R, Flavell R. JNK1 is required for T cell-mediated immunity against Leishmania major infection. J Immunol. 2000;165:2671-6 pubmed
    ..In the current study, we used Jnk1-deficient mice to examine the function of JNK during an in vivo pathogenic infection, leishmaniasis, which is ..
  56. Sabapathy K, Jochum W, Hochedlinger K, Chang L, Karin M, Wagner E. Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2. Mech Dev. 1999;89:115-24 pubmed
    Mice lacking both c-Jun-NH(2)-terminal kinases (JNK1 and JNK2) were generated to define their roles in development...
  57. Yang D, Tournier C, Wysk M, Lu H, Xu J, Davis R, et al. Targeted disruption of the MKK4 gene causes embryonic death, inhibition of c-Jun NH2-terminal kinase activation, and defects in AP-1 transcriptional activity. Proc Natl Acad Sci U S A. 1997;94:3004-9 pubmed
    ..kinase group of dual specificity protein kinases that functions as an activator of the c-Jun NH2-terminal kinase (JNK) in vitro...
  58. Hirosumi J, Tuncman G, Chang L, Gorgun C, Uysal K, Maeda K, et al. A central role for JNK in obesity and insulin resistance. Nature. 2002;420:333-6 pubmed
    ..Here we show that JNK activity is abnormally elevated in obesity. Furthermore, an absence of JNK1 results in decreased adiposity, significantly improved insulin sensitivity and enhanced insulin receptor signalling ..
  59. Hirai S, Kawaguchi A, Hirasawa R, Baba M, Ohnishi T, Ohno S. MAPK-upstream protein kinase (MUK) regulates the radial migration of immature neurons in telencephalon of mouse embryo. Development. 2002;129:4483-95 pubmed
    ..We show that the protein levels of a JNK activator kinase, MUK/DLK/ZPK, and JNK activity increase potently and temporally in newly generated neurons in ..
  60. Kaiser R, Liang Q, Bueno O, Huang Y, Lackey T, Klevitsky R, et al. Genetic inhibition or activation of JNK1/2 protects the myocardium from ischemia-reperfusion-induced cell death in vivo. J Biol Chem. 2005;280:32602-8 pubmed
    ..b>jnk1-/-, jnk2-/-, and transgenic mice expressing dominant negative JNK1/2 within the heart were each shown to have less ..
  61. Kuan C, Whitmarsh A, Yang D, Liao G, Schloemer A, Dong C, et al. A critical role of neural-specific JNK3 for ischemic apoptosis. Proc Natl Acad Sci U S A. 2003;100:15184-9 pubmed
    ..signaling is an important contributor to stress-induced apoptosis, but it is unclear whether JNK and its isoforms (JNK1, JNK2, and JNK3) have distinct roles in cerebral ischemia...
  62. Thiefes A, Wolter S, Mushinski J, Hoffmann E, Dittrich Breiholz O, Graue N, et al. Simultaneous blockade of NFkappaB, JNK, and p38 MAPK by a kinase-inactive mutant of the protein kinase TAK1 sensitizes cells to apoptosis and affects a distinct spectrum of tumor necrosis factor [corrected] target genes. J Biol Chem. 2005;280:27728-41 pubmed
    ..interleukin-1 was also suppressed in cells that expressed TAK1 antisense RNA or that were genetically deficient in JNK1/2 or p65 NFkappaB...
  63. Ventura J, Hübner A, Zhang C, Flavell R, Shokat K, Davis R. Chemical genetic analysis of the time course of signal transduction by JNK. Mol Cell. 2006;21:701-10 pubmed
    ..embryonic fibroblasts to tumor necrosis factor (TNF) causes biphasic activation of the c-Jun NH(2)-terminal kinase (JNK) signaling pathway...
  64. Sakurai T, Maeda S, Chang L, Karin M. Loss of hepatic NF-kappa B activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation. Proc Natl Acad Sci U S A. 2006;103:10544-51 pubmed
    ..Hepatocytes express both JNK1 and JNK2, but previous studies indicate that JNK1 is more important for hepatocyte proliferation...
  65. Oishi I, Suzuki H, Onishi N, Takada R, Kani S, Ohkawara B, et al. The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway. Genes Cells. 2003;8:645-54 pubmed
    ..Interestingly, Wnt5a and Ror2 activate the non-canonical Wnt pathway, as assessed by activation of JNK in cultured cells and inhibition of convergent extension movements in Xenopus...
  66. Hunot S, Vila M, Teismann P, Davis R, Hirsch E, Przedborski S, et al. JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease. Proc Natl Acad Sci U S A. 2004;101:665-70 pubmed
    ..Examination of various JNK-deficient mice shows that both JNK2 and JNK3, but not JNK1, are required for MPTP-induced c-Jun activation and dopaminergic cell demise...
  67. Dong C, Yang D, Tournier C, Whitmarsh A, Xu J, Davis R, et al. JNK is required for effector T-cell function but not for T-cell activation. Nature. 2000;405:91-4 pubmed
    ..Previously, we found that T cells from mice deficient in the Jnk1 or Jnk2 gene can be activated and produce IL-2 normally, but are deficient in functional differentiation into Th1 ..
  68. Ricci R, Sumara G, Sumara I, Rozenberg I, Kurrer M, Akhmedov A, et al. Requirement of JNK2 for scavenger receptor A-mediated foam cell formation in atherogenesis. Science. 2004;306:1558-61 pubmed
    ..We show that atherosclerosis-prone ApoE-/- mice simultaneously lacking JNK2 (ApoE-/- JNK2-/- mice), but not ApoE-/- JNK1-/- mice, developed less atherosclerosis than do ApoE-/- mice...
  69. Yoshimura K, Aoki H, Ikeda Y, Fujii K, Akiyama N, Furutani A, et al. Regression of abdominal aortic aneurysm by inhibition of c-Jun N-terminal kinase. Nat Med. 2005;11:1330-8 pubmed
    ..Here, we identify JNK as a proximal signaling molecule in the pathogenesis of AAA...
  70. Morse D, Otterbein L, Watkins S, Alber S, Zhou Z, Flavell R, et al. Deficiency in the c-Jun NH2-terminal kinase signaling pathway confers susceptibility to hyperoxic lung injury in mice. Am J Physiol Lung Cell Mol Physiol. 2003;285:L250-7 pubmed
    ..We examined the effect of Jnk1 gene deletion on in vivo responses to hyperoxia in mice...
  71. Sabapathy K, Hochedlinger K, Nam S, Bauer A, Karin M, Wagner E. Distinct roles for JNK1 and JNK2 in regulating JNK activity and c-Jun-dependent cell proliferation. Mol Cell. 2004;15:713-25 pubmed
    ..Although JNK1 and JNK2 were shown to differentially regulate fibroblast proliferation, the underlying mechanistic basis remains ..