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Gene Review

Mapk1  -  mitogen activated protein kinase 1

Rattus norvegicus

Synonyms: ERK-2, ERT1, Erk2, Extracellular signal-regulated kinase 2, MAP kinase 1, ...
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Disease relevance of Mapk1


Psychiatry related information on Mapk1


High impact information on Mapk1

  • However, the known cytoplasmic substrates for MEK1, ERK1, and ERK2 are not required for this process [11].
  • Activation mechanism of the MAP kinase ERK2 by dual phosphorylation [12].
  • The mitogen-activated protein (MAP) kinases Erk-1 and Erk-2 are proline-directed kinases that are themselves activated through concomitant phosphorylation of tyrosine and threonine residues [13].
  • The two domains of unphosphorylated ERK2 are farther apart than in the active conformation of cAMP-dependent protein kinase and the peptide-binding site is blocked by tyrosine 185, one of the two residues that are phosphorylated in the active enzyme [14].
  • These findings suggest that the MAPK signaling pathway promotes cell survival by a dual mechanism comprising the posttranslational modification and inactivation of a component of the cell death machinery and the increased transcription of pro-survival genes [15].

Chemical compound and disease context of Mapk1


Biological context of Mapk1


Anatomical context of Mapk1


Associations of Mapk1 with chemical compounds


Physical interactions of Mapk1


Enzymatic interactions of Mapk1


Regulatory relationships of Mapk1

  • Coexpression of kinase-deficient mutants of ERK1 and ERK2 inhibited the activation of AP-1 caused by expression of small t and either MEK1 or BXB [23].
  • MEK2/ERK2 activation in early G1 phase did not lead to cell proliferation but induced cell shape spreading and demonstration was provided that this MAPK-dependent spreading was required for reaching G1/S transition and DNA replication [41].
  • Vav overexpression resulted in the constitutive activation of JNK1 with little or no effect on p38 mitogen-activated protein kinase and ERK2 [42].
  • In contrast, ERK2 was highly activated by EGF treatment, but the magnitude of activation was significantly lower in hepatocytes of aged animals compared to those of young animals (7-fold versus 20-fold, respectively) [43].
  • Compared with ET-1, ET-3 stimulated only a rapid increase of p42 MAP kinase activity [44].

Other interactions of Mapk1


Analytical, diagnostic and therapeutic context of Mapk1

  • Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart. p38/RK mitogen-activated protein kinases and c-Jun N-terminal kinases are activated by ischemia/reperfusion [2].
  • Immunoblotting showed that the relative abundances of MAPK and MEK protein in ventricles declined to < 20% of their postpartal abundances after 50 days [29].
  • In retrogradely perfused hearts, high coronary perfusion pressure (120 mm Hg for 5 minutes), norepinephrine (50 mumol/L for 5 minutes), or isoproterenol (50 mumol/L for 5 minutes) stimulated MAPK and MEK approximately 2- to 5-fold [29].
  • Expression of components of the MAPK cascade were determined in tumor and adjacent, non-neoplastic liver specimens by Western blot analysis and functional activity confirmed by substrate phosphorylation assays [3].
  • ERK2 was mainly in the cytoplasm in resting cells but translocated into the nucleus after the ligation of IgE receptors [46].


  1. Induction of mitogen-activated protein kinase signal transduction pathway during gastric ulcer healing in rats. Pai, R., Ohta, M., Itani, R.M., Sarfeh, I.J., Tarnawski, A.S. Gastroenterology (1998) [Pubmed]
  2. Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart. p38/RK mitogen-activated protein kinases and c-Jun N-terminal kinases are activated by ischemia/reperfusion. Bogoyevitch, M.A., Gillespie-Brown, J., Ketterman, A.J., Fuller, S.J., Ben-Levy, R., Ashworth, A., Marshall, C.J., Sugden, P.H. Circ. Res. (1996) [Pubmed]
  3. Altered expression of mitogen-activated protein kinases in a rat model of experimental hepatocellular carcinoma. McKillop, I.H., Schmidt, C.M., Cahill, P.A., Sitzmann, J.V. Hepatology (1997) [Pubmed]
  4. Involvement of Ras and Raf in the Gi-coupled acetylcholine muscarinic m2 receptor activation of mitogen-activated protein (MAP) kinase kinase and MAP kinase. Winitz, S., Russell, M., Qian, N.X., Gardner, A., Dwyer, L., Johnson, G.L. J. Biol. Chem. (1993) [Pubmed]
  5. Dissociation of p44 and p42 mitogen-activated protein kinase activation from receptor-induced hypertrophy in neonatal rat ventricular myocytes. Post, G.R., Goldstein, D., Thuerauf, D.J., Glembotski, C.C., Brown, J.H. J. Biol. Chem. (1996) [Pubmed]
  6. Okadaic-acid-induced inhibition of protein phosphatase 2A produces activation of mitogen-activated protein kinases ERK1/2, MEK1/2, and p70 S6, similar to that in Alzheimer's disease. Pei, J.J., Gong, C.X., An, W.L., Winblad, B., Cowburn, R.F., Grundke-Iqbal, I., Iqbal, K. Am. J. Pathol. (2003) [Pubmed]
  7. Physical activity elicits sustained activation of the cyclic AMP response element-binding protein and mitogen-activated protein kinase in the rat hippocampus. Shen, H., Tong, L., Balazs, R., Cotman, C.W. Neuroscience (2001) [Pubmed]
  8. The MAPK cascade is required for mammalian associative learning. Atkins, C.M., Selcher, J.C., Petraitis, J.J., Trzaskos, J.M., Sweatt, J.D. Nat. Neurosci. (1998) [Pubmed]
  9. Differential activation of c-Jun N-terminal protein kinase and p38 in rat hippocampus and cerebellum after electroconvulsive shock. Oh, S.W., Ahn, Y.M., Kang, U.G., Kim, Y.S., Park, J.B. Neurosci. Lett. (1999) [Pubmed]
  10. Different hippocampal molecular requirements for short- and long-term retrieval of one-trial avoidance learning. Izquierdo, L.A., Barros, D.M., Ardenghi, P.G., Pereira, P., Rodrigues, C., Choi, H., Medina, J.H., Izquierdo, I. Behav. Brain Res. (2000) [Pubmed]
  11. Signaling via mitogen-activated protein kinase kinase (MEK1) is required for Golgi fragmentation during mitosis. Acharya, U., Mallabiabarrena, A., Acharya, J.K., Malhotra, V. Cell (1998) [Pubmed]
  12. Activation mechanism of the MAP kinase ERK2 by dual phosphorylation. Canagarajah, B.J., Khokhlatchev, A., Cobb, M.H., Goldsmith, E.J. Cell (1997) [Pubmed]
  13. The stress-activated protein kinase subfamily of c-Jun kinases. Kyriakis, J.M., Banerjee, P., Nikolakaki, E., Dai, T., Rubie, E.A., Ahmad, M.F., Avruch, J., Woodgett, J.R. Nature (1994) [Pubmed]
  14. Atomic structure of the MAP kinase ERK2 at 2.3 A resolution. Zhang, F., Strand, A., Robbins, D., Cobb, M.H., Goldsmith, E.J. Nature (1994) [Pubmed]
  15. Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Bonni, A., Brunet, A., West, A.E., Datta, S.R., Takasu, M.A., Greenberg, M.E. Science (1999) [Pubmed]
  16. Endothelin-1 induces serine phosphorylation of the adaptor protein p66Shc and its association with 14-3-3 protein in glomerular mesangial cells. Foschi, M., Franchi, F., Han, J., La Villa, G., Sorokin, A. J. Biol. Chem. (2001) [Pubmed]
  17. Effects of ethanol on mitogen-activated protein kinase and stress-activated protein kinase cascades in normal and regenerating liver. Chen, J., Ishac, E.J., Dent, P., Kunos, G., Gao, B. Biochem. J. (1998) [Pubmed]
  18. Androgens activate mitogen-activated protein kinase signaling: role in neuroprotection. Nguyen, T.V., Yao, M., Pike, C.J. J. Neurochem. (2005) [Pubmed]
  19. Activation of Stat1 and subsequent transcription of inducible nitric oxide synthase gene in C6 glioma cells is independent of interferon-gamma-induced MAPK activation that is mediated by p21ras. Nishiya, T., Uehara, T., Edamatsu, H., Kaziro, Y., Itoh, H., Nomura, Y. FEBS Lett. (1997) [Pubmed]
  20. Despite minimal hemodynamic alterations endotoxemia modulates NOS and p38-MAPK phosphorylation via metalloendopeptidases. Gupta, A., Sharma, A.C. Mol. Cell. Biochem. (2004) [Pubmed]
  21. D(2) dopamine receptors induce mitogen-activated protein kinase and cAMP response element-binding protein phosphorylation in neurons. Yan, Z., Feng, J., Fienberg, A.A., Greengard, P. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  22. Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in cardiomyocytes. Purcell, N.H., Darwis, D., Bueno, O.F., Müller, J.M., Schüle, R., Molkentin, J.D. Mol. Cell. Biol. (2004) [Pubmed]
  23. Simian virus 40 small t antigen cooperates with mitogen-activated kinases to stimulate AP-1 activity. Frost, J.A., Alberts, A.S., Sontag, E., Guan, K., Mumby, M.C., Feramisco, J.R. Mol. Cell. Biol. (1994) [Pubmed]
  24. H-Ras signaling and K-Ras signaling are differentially dependent on endocytosis. Roy, S., Wyse, B., Hancock, J.F. Mol. Cell. Biol. (2002) [Pubmed]
  25. Rapid mitogen-activated protein kinase activation by transforming growth factor alpha in wounded rat intestinal epithelial cells. Göke, M., Kanai, M., Lynch-Devaney, K., Podolsky, D.K. Gastroenterology (1998) [Pubmed]
  26. Mapping of atypical protein kinase C within the nerve growth factor signaling cascade: relationship to differentiation and survival of PC12 cells. Wooten, M.W., Seibenhener, M.L., Neidigh, K.B., Vandenplas, M.L. Mol. Cell. Biol. (2000) [Pubmed]
  27. Insulin signaling and its regulation of system A amino acid uptake in cultured rat vascular smooth muscle cells. Obata, T., Kashiwagi, A., Maegawa, H., Nishio, Y., Ugi, S., Hidaka, H., Kikkawa, R. Circ. Res. (1996) [Pubmed]
  28. Caveolin-1 expression by means of p38beta mitogen-activated protein kinase mediates the antiproliferative effect of carbon monoxide. Kim, H.P., Wang, X., Nakao, A., Kim, S.I., Murase, N., Choi, M.E., Ryter, S.W., Choi, A.M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  29. Regulation of mitogen-activated protein kinase cascade in adult rat heart preparations in vitro. Lazou, A., Bogoyevitch, M.A., Clerk, A., Fuller, S.J., Marshall C, J., Sugden, P.H. Circ. Res. (1994) [Pubmed]
  30. Neurotransmitter- and growth factor-induced cAMP response element binding protein phosphorylation in glial cell progenitors: role of calcium ions, protein kinase C, and mitogen-activated protein kinase/ribosomal S6 kinase pathway. Pende, M., Fisher, T.L., Simpson, P.B., Russell, J.T., Blenis, J., Gallo, V. J. Neurosci. (1997) [Pubmed]
  31. Adhesion stimulates direct PAK1/ERK2 association and leads to ERK-dependent PAK1 Thr212 phosphorylation. Sundberg-Smith, L.J., Doherty, J.T., Mack, C.P., Taylor, J.M. J. Biol. Chem. (2005) [Pubmed]
  32. Characterization of epidermal growth factor receptor function in lysophosphatidic acid signaling in PC12 cells. Kim, S.N., Park, J.G., Lee, E.B., Kim, S.S., Yoo, Y.S. J. Cell. Biochem. (2000) [Pubmed]
  33. The mitogen-activated protein kinase cascade couples PKA and PKC to cAMP response element binding protein phosphorylation in area CA1 of hippocampus. Roberson, E.D., English, J.D., Adams, J.P., Selcher, J.C., Kondratick, C., Sweatt, J.D. J. Neurosci. (1999) [Pubmed]
  34. Cholecystokinin activates PYK2/CAKbeta by a phospholipase C-dependent mechanism and its association with the mitogen-activated protein kinase signaling pathway in pancreatic acinar cells. Tapia, J.A., Ferris, H.A., Jensen, R.T., García, L.J. J. Biol. Chem. (1999) [Pubmed]
  35. Effects of mitogen-activated protein kinase pathway and co-activator CREP-binding protein on peroxisome proliferator-activated receptor-gamma-mediated transcription suppression of angiotensin II type 1 receptor gene. Sugawara, A., Takeuchi, K., Uruno, A., Kudo, M., Sato, K., Ito, S. Hypertens. Res. (2003) [Pubmed]
  36. Differential activation of protein kinase C isoforms by endothelin-1 and phenylephrine and subsequent stimulation of p42 and p44 mitogen-activated protein kinases in ventricular myocytes cultured from neonatal rat hearts. Clerk, A., Bogoyevitch, M.A., Anderson, M.B., Sugden, P.H. J. Biol. Chem. (1994) [Pubmed]
  37. Pituitary adenylate cyclase activating polypeptide (PACAP) stimulates mitogen-activated protein kinase (MAPK) in cultured rat astrocytes. Moroo, I., Tatsuno, I., Uchida, D., Tanaka, T., Saito, J., Saito, Y., Hirai, A. Brain Res. (1998) [Pubmed]
  38. MAP kinase pathways involving hsp27 regulate fibroblast-mediated wound contraction. Hirano, S., Rees, R.S., Gilmont, R.R. J. Surg. Res. (2002) [Pubmed]
  39. Differential effects of the EGF family of growth factors on protein secretion, MAPK activation, and intracellular calcium concentration in rat lacrimal gland. Chen, L.L., Johansson, J.K., Hodges, R.R., Zoukhri, D., Ghinelli, E., Rios, J.D., Dartt, D.A. Exp. Eye Res. (2005) [Pubmed]
  40. The A-type potassium channel Kv4.2 is a substrate for the mitogen-activated protein kinase ERK. Adams, J.P., Anderson, A.E., Varga, A.W., Dineley, K.T., Cook, R.G., Pfaffinger, P.J., Sweatt, J.D. J. Neurochem. (2000) [Pubmed]
  41. Mechanism in the sequential control of cell morphology and S phase entry by epidermal growth factor involves distinct MEK/ERK activations. Rescan, C., Coutant, A., Talarmin, H., Theret, N., Glaise, D., Guguen-Guillouzo, C., Baffet, G. Mol. Biol. Cell (2001) [Pubmed]
  42. Tyrosine phosphorylation of Vav stimulates IL-6 production in mast cells by a Rac/c-Jun N-terminal kinase-dependent pathway. Song, J.S., Haleem-Smith, H., Arudchandran, R., Gomez, J., Scott, P.M., Mill, J.F., Tan, T.H., Rivera, J. J. Immunol. (1999) [Pubmed]
  43. Age-related decline in mitogen-activated protein kinase activity in epidermal growth factor-stimulated rat hepatocytes. Liu, Y., Guyton, K.Z., Gorospe, M., Xu, Q., Kokkonen, G.C., Mock, Y.D., Roth, G.S., Holbrook, N.J. J. Biol. Chem. (1996) [Pubmed]
  44. Endothelin stimulates mitogen-activated protein kinase activity in mesangial cells through ETA. Wang, Y., Pouysségur, J., Dunn, M.J. J. Am. Soc. Nephrol. (1994) [Pubmed]
  45. The role of protein kinase B and mitogen-activated protein kinase in epidermal growth factor and tumor necrosis factor alpha-mediated rat hepatocyte survival and apoptosis. Roberts, R.A., James, N.H., Cosulich, S.C. Hepatology (2000) [Pubmed]
  46. Nuclear shuttling of mitogen-activated protein (MAP) kinase (extracellular signal-regulated kinase (ERK) 2) was dynamically controlled by MAP/ERK kinase after antigen stimulation in RBL-2H3 cells. Furuno, T., Hirashima, N., Onizawa, S., Sagiya, N., Nakanishi, M. J. Immunol. (2001) [Pubmed]
  47. Dependence of peroxisome proliferator-activated receptor ligand-induced mitogen-activated protein kinase signaling on epidermal growth factor receptor transactivation. Gardner, O.S., Dewar, B.J., Earp, H.S., Samet, J.M., Graves, L.M. J. Biol. Chem. (2003) [Pubmed]
  48. Activation of Go-coupled dopamine D2 receptors inhibits ERK1/ERK2 in pituitary cells. A key step in the transcriptional suppression of the prolactin gene. Liu, J.C., Baker, R.E., Sun, C., Sundmark, V.C., Elsholtz, H.P. J. Biol. Chem. (2002) [Pubmed]
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