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Gene Review

Mapk1  -  mitogen-activated protein kinase 1

Mus musculus

Synonyms: 9030612K14Rik, AA407128, AU018647, C78273, ERK, ...
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Disease relevance of Mapk1


Psychiatry related information on Mapk1

  • Recent investigations have shown that three major striatal-signaling pathways (protein kinase A/DARPP-32, Akt/glycogen synthase kinase 3, and ERK) are involved in the regulation of locomotor activity by the monoaminergic neurotransmitter dopamine [6].
  • Our results reveal an unexpected complexity of ERK-dependent signaling in the brain and a critical regulatory role for ERK1 in the long-term adaptive changes underlying striatum-dependent behavioral plasticity and drug addiction [7].
  • Attention has focused on proline-directed serine/threonine kinases as mediating the cytoskeletal modifications of Alzheimer's disease, and we show that overexpression of APP can influence the activation of a candidate kinase, the mitogen-activated protein kinase (MAPK) [8].
  • To study how caloric intake after food deprivation influences intracellular signal transduction, we investigated the phosphorylation of ERK and p38 in the murine hypothalamus of refed mice [9].
  • Several functional groups, including mitogen-activated protein kinase signaling and transcription regulation pathways, were found to be significantly overrepresented and may play an important role in establishing a high level of voluntary alcohol drinking in these mouse models [10].

High impact information on Mapk1

  • Conditional expression of a dominant-negative form of MEK1 in the postnatal murine forebrain inhibited ERK activation and caused selective deficits in hippocampal memory retention and the translation-dependent, transcription-independent phase of hippocampal L-LTP [11].
  • We demonstrate herein a novel paradigm of sex steroid action on osteoblasts, osteocytes, embryonic fibroblasts, and HeLa cells involving activation of a Src/Shc/ERK signaling pathway and attenuating apoptosis [12].
  • SPP induces the Gi/mitogen-activated protein kinase/cell survival pathway and the small GTPase Rho- and Raccoupled adherens junction assembly [13].
  • This resulted in plasma membrane targeting of Sos and stimulation of the Ras signaling pathway, including ERK and AP-1 activities leading to oncogenic transformation [14].
  • 3CH134 blocks phosphorylation and activation of p42MAPK mediated by serum, oncogenic Ras, or activated Raf, whereas the catalytically inactive mutant of the phosphatase, Cys-258-->Ser, augments MAP kinase phosphorylation under similar conditions [15].

Chemical compound and disease context of Mapk1


Biological context of Mapk1


Anatomical context of Mapk1

  • In p44 MAPK-/- thymocytes, proliferation in response to activation with a monoclonal antibody to the T cell receptor in the presence of phorbol myristate acetate was severely reduced even though activation of p42 MAPK was more sustained in these cells [25].
  • Here, we report that beta1 integrin ligation on human natural killer (NK) cells results in the activation of Ras/mitogen-activated protein kinase pathways [26].
  • Fluid shear stress activation of egr-1 transcription in cultured human endothelial and epithelial cells is mediated via the extracellular signal-related kinase 1/2 mitogen-activated protein kinase pathway [27].
  • Consistent with a specific negative regulatory role for ERK in macrophages, chemical activation of this pathway in DCs suppressed CpG-DNA-induced IL-12 production [28].
  • We have analyzed the mitogen-activated protein kinase (MAPK) pathways triggered by CpG-DNA and their significance for cytokine production in two subsets of APCs, i.e. macrophages and dendritic cells (DCs) [28].

Associations of Mapk1 with chemical compounds


Physical interactions of Mapk1


Enzymatic interactions of Mapk1


Regulatory relationships of Mapk1


Other interactions of Mapk1


Analytical, diagnostic and therapeutic context of Mapk1


  1. Intravenous administration of MEK inhibitor U0126 affords brain protection against forebrain ischemia and focal cerebral ischemia. Namura, S., Iihara, K., Takami, S., Nagata, I., Kikuchi, H., Matsushita, K., Moskowitz, M.A., Bonventre, J.V., Alessandrini, A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  2. Targeting Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase in the Mutant (V600E) B-Raf Signaling Cascade Effectively Inhibits Melanoma Lung Metastases. Sharma, A., Tran, M.A., Liang, S., Sharma, A.K., Amin, S., Smith, C.D., Dong, C., Robertson, G.P. Cancer Res. (2006) [Pubmed]
  3. Microarray-assisted pathway analysis identifies mitogen-activated protein kinase signaling as a mediator of resistance to the green tea polyphenol epigallocatechin 3-gallate in her-2/neu-overexpressing breast cancer cells. Guo, S., Lu, J., Subramanian, A., Sonenshein, G.E. Cancer Res. (2006) [Pubmed]
  4. Focal adhesion kinase enhances signaling through the Shc/extracellular signal-regulated kinase pathway in anaplastic astrocytoma tumor biopsy samples. Hecker, T.P., Grammer, J.R., Gillespie, G.Y., Stewart, J., Gladson, C.L. Cancer Res. (2002) [Pubmed]
  5. A predominant role for inhibition of the adenylate cyclase/protein kinase A pathway in ERK activation by cannabinoid receptor 1 in N1E-115 neuroblastoma cells. Davis, M.I., Ronesi, J., Lovinger, D.M. J. Biol. Chem. (2003) [Pubmed]
  6. Paradoxical striatal cellular signaling responses to psychostimulants in hyperactive mice. Beaulieu, J.M., Sotnikova, T.D., Gainetdinov, R.R., Caron, M.G. J. Biol. Chem. (2006) [Pubmed]
  7. Knockout of ERK1 MAP kinase enhances synaptic plasticity in the striatum and facilitates striatal-mediated learning and memory. Mazzucchelli, C., Vantaggiato, C., Ciamei, A., Fasano, S., Pakhotin, P., Krezel, W., Welzl, H., Wolfer, D.P., Pagès, G., Valverde, O., Marowsky, A., Porrazzo, A., Orban, P.C., Maldonado, R., Ehrengruber, M.U., Cestari, V., Lipp, H.P., Chapman, P.F., Pouysségur, J., Brambilla, R. Neuron (2002) [Pubmed]
  8. Phosphorylation of mitogen-activated protein kinase is altered in neuroectodermal cells overexpressing the human amyloid precursor protein 751 isoform. Grant, S.M., Morinville, A., Maysinger, D., Szyf, M., Cuello, A.C. Brain Res. Mol. Brain Res. (1999) [Pubmed]
  9. Attenuation of fasting-induced phosphorylation of mitogen-activated protein kinases (ERK/p38) in the mouse hypothalamus in response to refeeding. Ueyama, E., Morikawa, Y., Yasuda, T., Senba, E. Neurosci. Lett. (2004) [Pubmed]
  10. Toward understanding the genetics of alcohol drinking through transcriptome meta-analysis. Mulligan, M.K., Ponomarev, I., Hitzemann, R.J., Belknap, J.K., Tabakoff, B., Harris, R.A., Crabbe, J.C., Blednov, Y.A., Grahame, N.J., Phillips, T.J., Finn, D.A., Hoffman, P.L., Iyer, V.R., Koob, G.F., Bergeson, S.E. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Translational control by MAPK signaling in long-term synaptic plasticity and memory. Kelleher, R.J., Govindarajan, A., Jung, H.Y., Kang, H., Tonegawa, S. Cell (2004) [Pubmed]
  12. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Kousteni, S., Bellido, T., Plotkin, L.I., O'Brien, C.A., Bodenner, D.L., Han, L., Han, K., DiGregorio, G.B., Katzenellenbogen, J.A., Katzenellenbogen, B.S., Roberson, P.K., Weinstein, R.S., Jilka, R.L., Manolagas, S.C. Cell (2001) [Pubmed]
  13. Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate. Lee, M.J., Thangada, S., Claffey, K.P., Ancellin, N., Liu, C.H., Kluk, M., Volpi, M., Sha'afi, R.I., Hla, T. Cell (1999) [Pubmed]
  14. Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathway. Aronheim, A., Engelberg, D., Li, N., al-Alawi, N., Schlessinger, J., Karin, M. Cell (1994) [Pubmed]
  15. MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Sun, H., Charles, C.H., Lau, L.F., Tonks, N.K. Cell (1993) [Pubmed]
  16. Role of a mitogen-activated protein kinase pathway in the induction of phase II detoxifying enzymes by chemicals. Yu, R., Lei, W., Mandlekar, S., Weber, M.J., Der, C.J., Wu, J., Kong, A.T. J. Biol. Chem. (1999) [Pubmed]
  17. Activation of extracellular signal-regulated kinases, NF-kappa B, and cyclic adenosine 5'-monophosphate response element-binding protein in lung neutrophils occurs by differing mechanisms after hemorrhage or endotoxemia. Abraham, E., Arcaroli, J., Shenkar, R. J. Immunol. (2001) [Pubmed]
  18. Angiotensin II-induced cardiac hypertrophy is associated with different mitogen-activated protein kinase activation in normotensive and hypertensive mice. Pellieux, C., Sauthier, T., Aubert, J.F., Brunner, H.R., Pedrazzini, T. J. Hypertens. (2000) [Pubmed]
  19. Cannabinoid-receptor-independent cell signalling by N-acylethanolamines. Berdyshev, E.V., Schmid, P.C., Krebsbach, R.J., Hillard, C.J., Huang, C., Chen, N., Dong, Z., Schmid, H.H. Biochem. J. (2001) [Pubmed]
  20. Docosahexaenoic acid attenuates mycotoxin-induced immunoglobulin a nephropathy, interleukin-6 transcription, and mitogen-activated protein kinase phosphorylation in mice. Jia, Q., Zhou, H.R., Bennink, M., Pestka, J.J. J. Nutr. (2004) [Pubmed]
  21. Role of MEKK1 in cell survival and activation of JNK and ERK pathways defined by targeted gene disruption. Yujiri, T., Sather, S., Fanger, G.R., Johnson, G.L. Science (1998) [Pubmed]
  22. Dual specificity phosphatase 1 (DUSP1) regulates a subset of LPS-induced genes and protects mice from lethal endotoxin shock. Hammer, M., Mages, J., Dietrich, H., Servatius, A., Howells, N., Cato, A.C., Lang, R. J. Exp. Med. (2006) [Pubmed]
  23. Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK. Allan, L.A., Morrice, N., Brady, S., Magee, G., Pathak, S., Clarke, P.R. Nat. Cell Biol. (2003) [Pubmed]
  24. Phenotypic reversion or death of cancer cells by altering signaling pathways in three-dimensional contexts. Wang, F., Hansen, R.K., Radisky, D., Yoneda, T., Barcellos-Hoff, M.H., Petersen, O.W., Turley, E.A., Bissell, M.J. J. Natl. Cancer Inst. (2002) [Pubmed]
  25. Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice. Pagès, G., Guérin, S., Grall, D., Bonino, F., Smith, A., Anjuere, F., Auberger, P., Pouysségur, J. Science (1999) [Pubmed]
  26. Integrin-mediated ras-extracellular regulated kinase (ERK) signaling regulates interferon gamma production in human natural killer cells. Mainiero, F., Gismondi, A., Soriani, A., Cippitelli, M., Palmieri, G., Jacobelli, J., Piccoli, M., Frati, L., Santoni, A. J. Exp. Med. (1998) [Pubmed]
  27. Fluid shear stress activation of egr-1 transcription in cultured human endothelial and epithelial cells is mediated via the extracellular signal-related kinase 1/2 mitogen-activated protein kinase pathway. Schwachtgen, J.L., Houston, P., Campbell, C., Sukhatme, V., Braddock, M. J. Clin. Invest. (1998) [Pubmed]
  28. Cell type-specific activation of mitogen-activated protein kinases by CpG-DNA controls interleukin-12 release from antigen-presenting cells. Häcker, H., Mischak, H., Häcker, G., Eser, S., Prenzel, N., Ullrich, A., Wagner, H. EMBO J. (1999) [Pubmed]
  29. Blockade of the epidermal growth factor receptor tyrosine kinase suppresses tumorigenesis in MMTV/Neu + MMTV/TGF-alpha bigenic mice. Lenferink, A.E., Simpson, J.F., Shawver, L.K., Coffey, R.J., Forbes, J.T., Arteaga, C.L. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  30. Mos/mitogen-activated protein kinase can induce early meiotic phenotypes in the absence of maturation-promoting factor: a novel system for analyzing spindle formation during meiosis I. Choi, T., Rulong, S., Resau, J., Fukasawa, K., Matten, W., Kuriyama, R., Mansour, S., Ahn, N., Vande Woude, G.F. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  31. Altered extracellular signal-regulated kinase signaling and glycogen metabolism in skeletal muscle from p90 ribosomal S6 kinase 2 knockout mice. Dufresne, S.D., Bjørbaek, C., El-Haschimi, K., Zhao, Y., Aschenbach, W.G., Moller, D.E., Goodyear, L.J. Mol. Cell. Biol. (2001) [Pubmed]
  32. ERK and mTOR signaling couple beta-adrenergic receptors to translation initiation machinery to gate induction of protein synthesis-dependent long-term potentiation. Gelinas, J.N., Banko, J.L., Hou, L., Sonenberg, N., Weeber, E.J., Klann, E., Nguyen, P.V. J. Biol. Chem. (2007) [Pubmed]
  33. ERK and the F-box protein betaTRCP target STAT1 for degradation. Soond, S.M., Townsend, P.A., Barry, S.P., Knight, R.A., Latchman, D.S., Stephanou, A. J. Biol. Chem. (2008) [Pubmed]
  34. Tumor necrosis factor alpha rapidly activates the mitogen-activated protein kinase (MAPK) cascade in a MAPK kinase kinase-dependent, c-Raf-1-independent fashion in mouse macrophages. Winston, B.W., Lange-Carter, C.A., Gardner, A.M., Johnson, G.L., Riches, D.W. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  35. Multiple mitogen-activated protein kinase signaling pathways connect the cot oncoprotein to the c-jun promoter and to cellular transformation. Chiariello, M., Marinissen, M.J., Gutkind, J.S. Mol. Cell. Biol. (2000) [Pubmed]
  36. Phosphoproteomic analysis of neurotrophin receptor TrkB signaling pathways in mouse brain. Semenov, A., Goldsteins, G., Castrén, E. Cell. Mol. Neurobiol. (2006) [Pubmed]
  37. Blocked Ras activation in anergic CD4+ T cells. Fields, P.E., Gajewski, T.F., Fitch, F.W. Science (1996) [Pubmed]
  38. A novel mitogen-activated protein kinase docking site in the N terminus of MEK5alpha organizes the components of the extracellular signal-regulated kinase 5 signaling pathway. Seyfried, J., Wang, X., Kharebava, G., Tournier, C. Mol. Cell. Biol. (2005) [Pubmed]
  39. MEK-1 phosphorylation by MEK kinase, Raf, and mitogen-activated protein kinase: analysis of phosphopeptides and regulation of activity. Gardner, A.M., Vaillancourt, R.R., Lange-Carter, C.A., Johnson, G.L. Mol. Biol. Cell (1994) [Pubmed]
  40. Phosphorylation of paxillin via the ERK mitogen-activated protein kinase cascade in EL4 thymoma cells. Ku, H., Meier, K.E. J. Biol. Chem. (2000) [Pubmed]
  41. Inactivation of p42 MAP kinase by protein phosphatase 2A and a protein tyrosine phosphatase, but not CL100, in various cell lines. Alessi, D.R., Gomez, N., Moorhead, G., Lewis, T., Keyse, S.M., Cohen, P. Curr. Biol. (1995) [Pubmed]
  42. Fgf10 expression identifies parabronchial smooth muscle cell progenitors and is required for their entry into the smooth muscle cell lineage. Mailleux, A.A., Kelly, R., Veltmaat, J.M., De Langhe, S.P., Zaffran, S., Thiery, J.P., Bellusci, S. Development (2005) [Pubmed]
  43. Interleukin-18 induces activation and association of p56(lck) and MAPK in a murine TH1 clone. Tsuji-Takayama, K., Matsumoto, S., Koide, K., Takeuchi, M., Ikeda, M., Ohta, T., Kurimoto, M. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  44. BMP4 supports self-renewal of embryonic stem cells by inhibiting mitogen-activated protein kinase pathways. Qi, X., Li, T.G., Hao, J., Hu, J., Wang, J., Simmons, H., Miura, S., Mishina, Y., Zhao, G.Q. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  45. Activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway by conventional, novel, and atypical protein kinase C isotypes. Schönwasser, D.C., Marais, R.M., Marshall, C.J., Parker, P.J. Mol. Cell. Biol. (1998) [Pubmed]
  46. Src homology 2 domain-containing inositol-5-phosphatase 1 (SHIP1) negatively regulates TLR4-mediated LPS response primarily through a phosphatase activity- and PI-3K-independent mechanism. An, H., Xu, H., Zhang, M., Zhou, J., Feng, T., Qian, C., Qi, R., Cao, X. Blood (2005) [Pubmed]
  47. Evaluation of the role of mitogen-activated protein kinases in the expression of inducible nitric oxide synthase by IFN-gamma and TNF-alpha in mouse macrophages. Chan, E.D., Winston, B.W., Uh, S.T., Wynes, M.W., Rose, D.M., Riches, D.W. J. Immunol. (1999) [Pubmed]
  48. CrkL mediates Ras-dependent activation of the Raf/ERK pathway through the guanine nucleotide exchange factor C3G in hematopoietic cells stimulated with erythropoietin or interleukin-3. Nosaka, Y., Arai, A., Miyasaka, N., Miura, O. J. Biol. Chem. (1999) [Pubmed]
  49. Activation of extracellular signal-regulated kinase, ERK2, by p21ras oncoprotein. Leevers, S.J., Marshall, C.J. EMBO J. (1992) [Pubmed]
  50. The Sos1 and Sos2 Ras-specific exchange factors: differences in placental expression and signaling properties. Qian, X., Esteban, L., Vass, W.C., Upadhyaya, C., Papageorge, A.G., Yienger, K., Ward, J.M., Lowy, D.R., Santos, E. EMBO J. (2000) [Pubmed]
  51. Shortage of mitogen-activated protein kinase is responsible for resistance to AP-1 transactivation and transformation in mouse JB6 cells. Huang, C., Ma, W.Y., Young, M.R., Colburn, N., Dong, Z. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  52. Spatial and temporal patterns of ERK signaling during mouse embryogenesis. Corson, L.B., Yamanaka, Y., Lai, K.M., Rossant, J. Development (2003) [Pubmed]
  53. Extracellular signal-regulated kinase activated by epidermal growth factor and cell adhesion interacts with and phosphorylates vinexin. Mitsushima, M., Suwa, A., Amachi, T., Ueda, K., Kioka, N. J. Biol. Chem. (2004) [Pubmed]
  54. Murine hepatitis virus strain 3 induces the macrophage prothrombinase fgl-2 through p38 mitogen-activated protein kinase activation. McGilvray, I.D., Lu, Z., Wei, A.C., Dackiw, A.P., Marshall, J.C., Kapus, A., Levy, G., Rotstein, O.D. J. Biol. Chem. (1998) [Pubmed]
  55. Stimulation of stress-activated protein kinase and p38 HOG1 kinase in murine keratinocytes following photodynamic therapy with benzoporphyrin derivative. Tao, J., Sanghera, J.S., Pelech, S.L., Wong, G., Levy, J.G. J. Biol. Chem. (1996) [Pubmed]
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