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Gene Review

MAPK1  -  mitogen-activated protein kinase 1

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Disease relevance of MAPK1

  • This effect was blocked by pretreatment with pertussis toxin, suggesting that G alpha(i) plays an important role in mediating EG-VEGF-induced activation of MAPK signaling [1].
  • Our finding support the importance of specific PKC isozyme linked to MAPK pathway in the regulation of endothelial responses to hypoxia [2].
  • It is concluded that alpha BC phosphorylation during ischemia is regulated by p38 MAPK but not by ERK 1/2 [3].
  • Our previous studies have shown that 5-hydroxytryptamine (5-HT) induces cellular hyperplasia/hypertrophy through protein tyrosine phosphorylation, rapid formation of superoxide (O(2)(-)), and extracellular signal-regulated kinase (ERK)1/ERK2 mitogen-activated protein (MAP) kinase activation [4].
  • Infection of BPASMCs with an adenovirus containing catalase inhibited both ERK1/ERK2 MAP kinase activation and DNA synthesis induced by 5-HT [4].

High impact information on MAPK1


Chemical compound and disease context of MAPK1

  • These data suggest that Ang II stimulates Src tyrosine kinase via a pertussis toxin-sensitive pathway, which in turn activates the MAPK pathway, resulting in increased eNOS protein expression in BPAECs [10].
  • A major component of Ang II-induced MAPK activation was insensitive to pertussis toxin (PTX), although a minor PTX-sensitive component could not be excluded [11].

Biological context of MAPK1

  • The p38 kinase inhibitor SB203580 (20 microM, 30 min) abolished Ser31 and Ser19 phosphorylation on TOH and partially inhibited ERK2 phosphorylation produced by AII [12].
  • The data also indicate that the methyl Se-specific inhibitory effects on these proteins are rapid and primary actions, preceding or independent of inhibitory effects on mitogenic signaling at the level of MAPK1/2 and on cell growth and survival [13].
  • Thus, this study demonstrates a novel role for the uPAR in endothelial cell signal transduction that involves the activation of FAK and MAPK, which are mediated by the receptor-binding domain of uPA [14].
  • MEK1 inhibition resulted in lower levels of ERK2 activation and synthesis and higher levels of apoptosis [15].
  • Incubation of EC with PD 98059, a specific mitogen-activated protein kinase kinase inhibitor, or transfection with Y185F, a dominant negative ERK2, strongly inhibited VEGF-activated JNK [16].

Anatomical context of MAPK1


Associations of MAPK1 with chemical compounds

  • KN93 also prevented H(2)O(2) activation of p38 MAPK [17].
  • Using two-dimensional immunoblotting we demonstrate that thrombin stimulation leads to increases in the tyrosine phosphorylation of 4 proteins, three different isoforms of P44 mitogen activated protein kinase (MAPK) and one isoform of P38 stress activated protein kinase (SAPK) [22].
  • Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor [23].
  • Ang II markedly inhibited DAX-1 protein expression in a time- and concentration-dependent manner (to 38.7 +/- 12.9% of controls at 3 nm after 6 h, p < 0.01), an effect that required de novo protein synthesis and ERK2/1 activation [24].
  • Insulin-induced desensitization could be prevented if a specific inhibitor of phosphatidylinositol 3-kinase (LY294002), but not an inhibitor of mitogen-activated protein kinase (PD98059), was present during the preincubation period [25].

Enzymatic interactions of MAPK1


Regulatory relationships of MAPK1


Other interactions of MAPK1


Analytical, diagnostic and therapeutic context of MAPK1


  1. Characterization of endocrine gland-derived vascular endothelial growth factor signaling in adrenal cortex capillary endothelial cells. Lin, R., LeCouter, J., Kowalski, J., Ferrara, N. J. Biol. Chem. (2002) [Pubmed]
  2. Endothelial exposure to hypoxia induces Egr-1 expression involving PKCalpha-mediated Ras/Raf-1/ERK1/2 pathway. Lo, L.W., Cheng, J.J., Chiu, J.J., Wung, B.S., Liu, Y.C., Wang, D.L. J. Cell. Physiol. (2001) [Pubmed]
  3. Differential translocation or phosphorylation of alpha B crystallin cannot be detected in ischemically preconditioned rabbit cardiomyocytes. Armstrong, S.C., Shivell, C.L., Ganote, C.E. J. Mol. Cell. Cardiol. (2000) [Pubmed]
  4. H(2)O(2) signals 5-HT-induced ERK MAP kinase activation and mitogenesis of smooth muscle cells. Lee, S.L., Simon, A.R., Wang, W.W., Fanburg, B.L. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  5. Thrombin-induced mitogenesis in coronary artery smooth muscle cells is potentiated by thromboxane A2 and involves upregulation of thromboxane receptor mRNA. Zucker, T.P., Bönisch, D., Muck, S., Weber, A.A., Bretschneider, E., Glusa, E., Schrör, K. Circulation (1998) [Pubmed]
  6. The cis-acting phorbol ester "12-O-tetradecanoylphorbol 13-acetate"-responsive element is involved in shear stress-induced monocyte chemotactic protein 1 gene expression. Shyy, J.Y., Lin, M.C., Han, J., Lu, Y., Petrime, M., Chien, S. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  7. Novel nuclear target for thrombin: activation of the Elk1 transcription factor leads to chemokine gene expression. Li, Q.J., Vaingankar, S., Sladek, F.M., Martins-Green, M. Blood (2000) [Pubmed]
  8. The Ras-JNK pathway is involved in shear-induced gene expression. Li, Y.S., Shyy, J.Y., Li, S., Lee, J., Su, B., Karin, M., Chien, S. Mol. Cell. Biol. (1996) [Pubmed]
  9. The fumagillin analogue TNP-470 inhibits DNA synthesis of vascular smooth muscle cells stimulated by platelet-derived growth factor and insulin-like growth factor-I. Possible involvement of cyclin-dependent kinase 2. Koyama, H., Nishizawa, Y., Hosoi, M., Fukumoto, S., Kogawa, K., Shioi, A., Morii, H. Circ. Res. (1996) [Pubmed]
  10. Src kinase mediates angiotensin II-dependent increase in pulmonary endothelial nitric oxide synthase. Li, X., Lerea, K.M., Li, J., Olson, S.C. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
  11. Angiotensin II activates mitogen-activated protein kinase via protein kinase C and Ras/Raf-1 kinase in bovine adrenal glomerulosa cells. Tian, Y., Smith, R.D., Balla, T., Catt, K.J. Endocrinology (1998) [Pubmed]
  12. Tyrosine hydroxylase phosphorylation in bovine adrenal chromaffin cells: the role of MAPKs after angiotensin II stimulation. Bobrovskaya, L., Odell, A., Leal, R.B., Dunkley, P.R. J. Neurochem. (2001) [Pubmed]
  13. Monomethyl selenium--specific inhibition of MMP-2 and VEGF expression: implications for angiogenic switch regulation. Jiang, C., Ganther, H., Lu, J. Mol. Carcinog. (2000) [Pubmed]
  14. The urokinase-type plasminogen activator receptor mediates tyrosine phosphorylation of focal adhesion proteins and activation of mitogen-activated protein kinase in cultured endothelial cells. Tang, H., Kerins, D.M., Hao, Q., Inagami, T., Vaughan, D.E. J. Biol. Chem. (1998) [Pubmed]
  15. Endogenous FGF1-induced activation and synthesis of extracellular signal-regulated kinase 2 reduce cell apoptosis in retinal-pigmented epithelial cells. Guillonneau, X., Bryckaert, M., Launay-Longo, C., Courtois, Y., Mascarelli, F. J. Biol. Chem. (1998) [Pubmed]
  16. Extracellular signal-regulated protein kinase/Jun kinase cross-talk underlies vascular endothelial cell growth factor-induced endothelial cell proliferation. Pedram, A., Razandi, M., Levin, E.R. J. Biol. Chem. (1998) [Pubmed]
  17. Role of CaMKII in hydrogen peroxide activation of ERK1/2, p38 MAPK, HSP27 and actin reorganization in endothelial cells. Nguyen, A., Chen, P., Cai, H. FEBS Lett. (2004) [Pubmed]
  18. The PKCalpha-D294G mutant found in pituitary and thyroid tumors fails to transduce extracellular signals. Zhu, Y., Dong, Q., Tan, B.J., Lim, W.G., Zhou, S., Duan, W. Cancer Res. (2005) [Pubmed]
  19. Histamine antagonizes serotonin and growth factor-induced mitogen-activated protein kinase activation in bovine tracheal smooth muscle cells. Hershenson, M.B., Chao, T.S., Abe, M.K., Gomes, I., Kelleher, M.D., Solway, J., Rosner, M.R. J. Biol. Chem. (1995) [Pubmed]
  20. Potential role for ceramide in mitogen-activated protein kinase activation and proliferation of vascular smooth muscle cells induced by oxidized low density lipoprotein. Augé, N., Escargueil-Blanc, I., Lajoie-Mazenc, I., Suc, I., Andrieu-Abadie, N., Pieraggi, M.T., Chatelut, M., Thiers, J.C., Jaffrézou, J.P., Laurent, G., Levade, T., Nègre-Salvayre, A., Salvayre, R. J. Biol. Chem. (1998) [Pubmed]
  21. SB 203580 inhibits p38 mitogen-activated protein kinase, nitric oxide production, and inducible nitric oxide synthase in bovine cartilage-derived chondrocytes. Badger, A.M., Cook, M.N., Lark, M.W., Newman-Tarr, T.M., Swift, B.A., Nelson, A.H., Barone, F.C., Kumar, S. J. Immunol. (1998) [Pubmed]
  22. Thrombin contraction of vascular smooth muscle: implications for vasospasm. Knoepp, L., Bagwell, C.D., Garlich, P., Brophy, C.M. International journal of surgical investigation. (1999) [Pubmed]
  23. Induction of endothelin-1 expression by glucose: an effect of protein kinase C activation. Park, J.Y., Takahara, N., Gabriele, A., Chou, E., Naruse, K., Suzuma, K., Yamauchi, T., Ha, S.W., Meier, M., Rhodes, C.J., King, G.L. Diabetes (2000) [Pubmed]
  24. Repression of DAX-1 and induction of SF-1 expression. Two mechanisms contributing to the activation of aldosterone biosynthesis in adrenal glomerulosa cells. Osman, H., Murigande, C., Nadakal, A., Capponi, A.M. J. Biol. Chem. (2002) [Pubmed]
  25. Insulin and interleukin-4 induce desensitization to the mitogenic effects of insulin-like growth factor-I. Pivotal role for insulin receptor substrate-2. Haddad, T.C., Conover, C.A. J. Biol. Chem. (1997) [Pubmed]
  26. Caveolin-1 is transiently dephosphorylated by shear stress-activated protein tyrosine phosphatase mu. Shin, J., Jo, H., Park, H. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  27. Homologous up-regulation of KDR/Flk-1 receptor expression by vascular endothelial growth factor in vitro. Shen, B.Q., Lee, D.Y., Gerber, H.P., Keyt, B.A., Ferrara, N., Zioncheck, T.F. J. Biol. Chem. (1998) [Pubmed]
  28. Phosphorylation and activation of protamine kinase by two forms of a myelin basic protein kinase from extracts of bovine kidney cortex. Reddy, S.A., Guo, H., Tarun, S.Z., Damuni, Z. J. Biol. Chem. (1993) [Pubmed]
  29. Protein kinase C mediates basic fibroblast growth factor-induced proliferation through mitogen-activated protein kinase in coronary smooth muscle cells. Skaletz-Rorowski, A., Waltenberger, J., Müller, J.G., Pawlus, E., Pinkernell, K., Breithardt, G. Arterioscler. Thromb. Vasc. Biol. (1999) [Pubmed]
  30. Akt-dependent phosphorylation of serine 1179 and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 cooperatively mediate activation of the endothelial nitric-oxide synthase by hydrogen peroxide. Cai, H., Li, Z., Davis, M.E., Kanner, W., Harrison, D.G., Dudley, S.C. Mol. Pharmacol. (2003) [Pubmed]
  31. Both FGF1 and bcl-x synthesis are necessary for the reduction of apoptosis in retinal pigmented epithelial cells by FGF2: role of the extracellular signal-regulated kinase 2. Bryckaert, M., Guillonneau, X., Hecquet, C., Courtois, Y., Mascarelli, F. Oncogene (1999) [Pubmed]
  32. Myristoylated alanine-rich C kinase substrate (MARCKS), a major protein kinase C substrate, is an in vivo substrate of proline-directed protein kinase(s). A mass spectroscopic analysis of the post-translational modifications. Taniguchi, H., Manenti, S., Suzuki, M., Titani, K. J. Biol. Chem. (1994) [Pubmed]
  33. Inhibition of phosphatidylinositol-3 kinase/Akt or mitogen-activated protein kinase signaling sensitizes endothelial cells to TNF-alpha cytotoxicity. Zhang, L., Himi, T., Morita, I., Murota, S. Cell Death Differ. (2001) [Pubmed]
  34. Molecular cloning and characterization of a mitogen-activated protein kinase-associated intracellular chloride channel. Qian, Z., Okuhara, D., Abe, M.K., Rosner, M.R. J. Biol. Chem. (1999) [Pubmed]
  35. Role of extracellular signal-regulated protein kinases 1 and 2 in oligodendroglial process extension. Stariha, R.L., Kikuchi, S., Siow, Y.L., Pelech, S.L., Kim, M., Kim, S.U. J. Neurochem. (1997) [Pubmed]
  36. Phosphatase resistance of ERK2 brain kinase PK40erk2. Roder, H.M., Hoffman, F.J., Schröder, W. J. Neurochem. (1995) [Pubmed]
  37. Renaturation and partial peptide sequencing of mitogen-activated protein kinase (MAP kinase) activator from rabbit skeletal muscle. Wu, J., Michel, H., Rossomando, A., Haystead, T., Shabanowitz, J., Hunt, D.F., Sturgill, T.W. Biochem. J. (1992) [Pubmed]
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