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Gene Review

MAPK11  -  mitogen-activated protein kinase 11

Homo sapiens

Synonyms: MAP kinase 11, MAP kinase p38 beta, MAPK 11, Mitogen-activated protein kinase 11, Mitogen-activated protein kinase p38 beta, ...
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Disease relevance of MAPK11


High impact information on MAPK11

  • Selective activation of the p38 MAP kinase (=SAPK2) pathway by MAP kinase kinase 6 induced mRNA stabilization [5].
  • We conclude that the HSP27-dependent actin polymerization-generating activity of SAPK2 associated with a misassembly of the focal adhesions is responsible for induction of membrane blebbing by stressing agents [2].
  • SAPK2/p38-dependent F-actin reorganization regulates early membrane blebbing during stress-induced apoptosis [2].
  • Cis-platinum, which activated SAPK2 but induced little ERK activity, also induced membrane blebbing that was dependent on the expression of HSP27 [2].
  • Our results suggest that cellular functions previously attributed to SAPK1 and/or SAPK2 may be mediated by SAPK3 [6].

Biological context of MAPK11

  • Overexpression of SAPK2 also stimulated PDX1-dependent transcription of a -50 to -250 region of the human insulin gene promoter linked to a firefly luciferase reporter gene [7].
  • Although p38-2 and p38 phosphorylate the same substrates, the site specificity of phosphorylation can differ as shown by two-dimensional phosphopeptide analysis of Sap-1a [8].
  • In conclusion, p38-2 may be an important component of the stress response required for the homeostasis of a cell [8].
  • In contrast, selenite-induced apoptotic DNA fragmentation was observed in the absence of these changes, but was associated with the phosphorylation of c-Jun-NH2-terminal kinase 1/2 and p38 mitogen-activated protein kinase/stress-activated protein kinase 2 [9].
  • Glucose-stimulated preproinsulin gene expression and nuclear trans-location of pancreatic duodenum homeobox-1 require activation of phosphatidylinositol 3-kinase but not p38 MAPK/SAPK2 [10].

Anatomical context of MAPK11

  • Epidermal growth factor stimulation of trophoblast differentiation requires MAPK11/14 (p38 MAP kinase) activation [11].
  • Here, we provide evidence that disruption of the microtubule structure rapidly triggers extracellular signal-regulated kinase (ERK) activation, whereas it was without effect on SAPK2 activity, which is commonly acknowledged to control pro-inflammatory cytokine production [12].
  • Moreover, a recombinant E-selectin/Fc chimera quickly increased the activation of SAPK2/p38 in HT-29 cells [13].
  • In turn, this triggers the activation of the SAPK2/p38 MAP kinase module, and promotes stress fiber formation and endothelial cell migration [14].
  • Similarly, HeLa cells stably expressing a kinase-inactive mutant of SAPK2/p38 showed a decreased capacity to cross a layer of HUVEC [13].

Associations of MAPK11 with chemical compounds

  • Unlike SAPK2, SAPK3 was not inhibited by the drug SB 203580 [6].
  • Our results indicate that high glucose (a cellular stress) activates SAPK2 by a novel mechanism in which a wortmannin/LY 294002-sensitive component plays an essential role [1].
  • Inhibiting protein degradation with MG132 caused the constitutive activation of SAPK2/p38, which was blocked by a pretreatment with either cycloheximide or heat shock [15].
  • We conclude that egr-1 induction by anisomycin is mediated by p38/SAPK2 and probably by MSK1 [16].
  • The effects of insulin were inhibited by the PtdIns 3-kinase inhibitors wortmannin and LY294002 and by the SAPK2 inhibitor SB203580, suggesting that its effects were mediated via activation of PtdIns 3-kinase and SAPK2 [17].

Regulatory relationships of MAPK11

  • SAPK2 then activates IUF1 indirectly by activating a novel IUF1-activating enzyme [1].

Other interactions of MAPK11


Analytical, diagnostic and therapeutic context of MAPK11

  • We report the molecular cloning of a novel isoform of p38 MAP kinase, p38 beta 2 [20].
  • For six selected genes, p38/SAPK2-regulated expression was confirmed and further analysed by Northern blot experiments, demonstrating a complex regulation of these genes under stress conditions [21].


  1. The p38/reactivating kinase mitogen-activated protein kinase cascade mediates the activation of the transcription factor insulin upstream factor 1 and insulin gene transcription by high glucose in pancreatic beta-cells. Macfarlane, W.M., Smith, S.B., James, R.F., Clifton, A.D., Doza, Y.N., Cohen, P., Docherty, K. J. Biol. Chem. (1997) [Pubmed]
  2. SAPK2/p38-dependent F-actin reorganization regulates early membrane blebbing during stress-induced apoptosis. Huot, J., Houle, F., Rousseau, S., Deschesnes, R.G., Shah, G.M., Landry, J. J. Cell Biol. (1998) [Pubmed]
  3. The Epstein-Barr virus latent membrane protein 1 induces interleukin-10 in Burkitt's lymphoma cells but not in Hodgkin's cells involving the p38/SAPK2 pathway. Vockerodt, M., Haier, B., Buttgereit, P., Tesch, H., Kube, D. Virology (2001) [Pubmed]
  4. Curcumin inhibits ultraviolet light induced human immunodeficiency virus gene expression. Taher, M.M., Lammering, G., Hershey, C., Valerie, K. Mol. Cell. Biochem. (2003) [Pubmed]
  5. The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism. Winzen, R., Kracht, M., Ritter, B., Wilhelm, A., Chen, C.Y., Shyu, A.B., Müller, M., Gaestel, M., Resch, K., Holtmann, H. EMBO J. (1999) [Pubmed]
  6. Activation of stress-activated protein kinase-3 (SAPK3) by cytokines and cellular stresses is mediated via SAPKK3 (MKK6); comparison of the specificities of SAPK3 and SAPK2 (RK/p38). Cuenda, A., Cohen, P., Buée-Scherrer, V., Goedert, M. EMBO J. (1997) [Pubmed]
  7. Glucose stimulates translocation of the homeodomain transcription factor PDX1 from the cytoplasm to the nucleus in pancreatic beta-cells. Macfarlane, W.M., McKinnon, C.M., Felton-Edkins, Z.A., Cragg, H., James, R.F., Docherty, K. J. Biol. Chem. (1999) [Pubmed]
  8. p38-2, a novel mitogen-activated protein kinase with distinct properties. Stein, B., Yang, M.X., Young, D.B., Janknecht, R., Hunter, T., Murray, B.W., Barbosa, M.S. J. Biol. Chem. (1997) [Pubmed]
  9. Caspases as key executors of methyl selenium-induced apoptosis (anoikis) of DU-145 prostate cancer cells. Jiang, C., Wang, Z., Ganther, H., Lu, J. Cancer Res. (2001) [Pubmed]
  10. Glucose-stimulated preproinsulin gene expression and nuclear trans-location of pancreatic duodenum homeobox-1 require activation of phosphatidylinositol 3-kinase but not p38 MAPK/SAPK2. Rafiq, I., da Silva Xavier, G., Hooper, S., Rutter, G.A. J. Biol. Chem. (2000) [Pubmed]
  11. Epidermal growth factor stimulation of trophoblast differentiation requires MAPK11/14 (p38 MAP kinase) activation. Johnstone, E.D., Sibley, C.P., Lowen, B., Guilbert, L.J. Biol. Reprod. (2005) [Pubmed]
  12. Microtubule integrity regulates src-like and extracellular signal-regulated kinase activities in human pro-monocytic cells. Importance for interleukin-1 production. Schmid-Alliana, A., Menou, L., Manié, S., Schmid-Antomarchi, H., Millet, M.A., Giuriato, S., Ferrua, B., Rossi, B. J. Biol. Chem. (1998) [Pubmed]
  13. Transendothelial migration of colon carcinoma cells requires expression of E-selectin by endothelial cells and activation of stress-activated protein kinase-2 (SAPK2/p38) in the tumor cells. Laferriere, J., Houle, F., Taher, M.M., Valerie, K., Huot, J. J. Biol. Chem. (2001) [Pubmed]
  14. Phosphorylation of Tyr1214 within VEGFR-2 Triggers the Recruitment of Nck and Activation of Fyn Leading to SAPK2/p38 Activation and Endothelial Cell Migration in Response to VEGF. Lamalice, L., Houle, F., Huot, J. J. Biol. Chem. (2006) [Pubmed]
  15. A short lived protein involved in the heat shock sensing mechanism responsible for stress-activated protein kinase 2 (SAPK2/p38) activation. Dorion, S., Bérubé, J., Huot, J., Landry, J. J. Biol. Chem. (1999) [Pubmed]
  16. Stress-induced stimulation of early growth response gene-1 by p38/stress-activated protein kinase 2 is mediated by a cAMP-responsive promoter element in a MAPKAP kinase 2-independent manner. Rolli, M., Kotlyarov, A., Sakamoto, K.M., Gaestel, M., Neininger, A. J. Biol. Chem. (1999) [Pubmed]
  17. Insulin stimulates pancreatic-duodenal homoeobox factor-1 (PDX1) DNA-binding activity and insulin promoter activity in pancreatic beta cells. Wu, H., MacFarlane, W.M., Tadayyon, M., Arch, J.R., James, R.F., Docherty, K. Biochem. J. (1999) [Pubmed]
  18. Promyelocytic leukemia is a direct inhibitor of SAPK2/p38 mitogen-activated protein kinase. Shin, J., Park, B., Cho, S., Lee, S., Kim, Y., Lee, S.O., Cho, K., Lee, S., Jin, B.S., Ahn, J.H., Choi, E.J., Ahn, K. J. Biol. Chem. (2004) [Pubmed]
  19. Cellular stresses and cytokines activate multiple mitogen-activated-protein kinase kinase homologues in PC12 and KB cells. Meier, R., Rouse, J., Cuenda, A., Nebreda, A.R., Cohen, P. Eur. J. Biochem. (1996) [Pubmed]
  20. Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6. Enslen, H., Raingeaud, J., Davis, R.J. J. Biol. Chem. (1998) [Pubmed]
  21. p38/SAPK2-dependent gene expression in Jurkat T cells. Rolli-Derkinderen, M., Gaestel, M. Biol. Chem. (2000) [Pubmed]
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