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Gene Review

MAPK6  -  mitogen-activated protein kinase 6

Homo sapiens

Synonyms: ERK-3, ERK3, Extracellular signal-regulated kinase 3, HsT17250, MAP kinase 6, ...
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Disease relevance of MAPK6


High impact information on MAPK6

  • N-Terminal ubiquitination of extracellular signal-regulated kinase 3 and p21 directs their degradation by the proteasome [4].
  • Importantly, we identified a fusion peptide between the N-terminal methionine of ERK3 and the C-terminal glycine of ubiquitin in vivo by tandem mass spectrometry analysis [4].
  • These findings demonstrate that ERK3 is conjugated to ubiquitin via its free NH(2) terminus [4].
  • To explore the molecular diversity of the ERK-3 subfamily, we isolated a novel human cDNA, designated Hu-ERK-3, from a fetal skeletal muscle library [5].
  • Finally, cell cycle synchronization studies revealed that the subcellular localization of ERK3 is temporally regulated [6].

Biological context of MAPK6


Anatomical context of MAPK6

  • In the present study, expression of p97MAPK was unique among the ERK family in that its expression was induced when human carcinoma cell lines are plated on type IV collagen [1].
  • Although expression of p97MAPK was detected in all of the tissues tested by Northern (RNA) analysis, the most abundant expression was seen in skeletal muscle [5].
  • Importantly, we show that enforced localization of ERK3 in the nucleus or cytoplasm markedly attenuates the ability of the kinase to induce cell cycle arrest in fibroblasts [9].
  • In contrast, ERK3 was restricted to the distal lung epithelium during the pseudoglandular phase (E17) but shifted to the proximal airways, particularly Clara cells during the saccular stage (E21) [11].
  • Overexpression of ERK-3 was correlated to TNM staging (average ratio of integral optic density (IOD)(tumor): IOD(normal) in TNM I, II, III, IV tumors was 1.43+/-0.34, 5.08+/-3.74, 4.99+/-1.08, 1.44+/-1.02, n = 42, P = 0.023) and serosa invasion (4.31+/-4.34 vs 2.00+/-2.03, P = 0.037) [12].

Associations of MAPK6 with chemical compounds


Other interactions of MAPK6


Analytical, diagnostic and therapeutic context of MAPK6


  1. Induction of p97MAPK expression regulates collagen mediated inhibition of proliferation and migration in human squamous cell carcinoma lines. Crowe, D.L. Int. J. Oncol. (2004) [Pubmed]
  2. Primary structure, expression and chromosomal locus of a human homolog of rat ERK3. Meloche, S., Beatty, B.G., Pellerin, J. Oncogene (1996) [Pubmed]
  3. Molecular cloning, isolation and characterisation of ERK3 gene from chewing-tobacco induced oral squamous cell carcinoma. Rai, R., Mahale, A., Saranath, D. Oral Oncol. (2004) [Pubmed]
  4. N-Terminal ubiquitination of extracellular signal-regulated kinase 3 and p21 directs their degradation by the proteasome. Coulombe, P., Rodier, G., Bonneil, E., Thibault, P., Meloche, S. Mol. Cell. Biol. (2004) [Pubmed]
  5. Cloning and characterization of p97MAPK, a novel human homolog of rat ERK-3. Zhu, A.X., Zhao, Y., Moller, D.E., Flier, J.S. Mol. Cell. Biol. (1994) [Pubmed]
  6. A novel mechanism for mitogen-activated protein kinase localization. Bind, E., Kleyner, Y., Skowronska-Krawczyk, D., Bien, E., Dynlacht, B.D., Sánchez, I. Mol. Biol. Cell (2004) [Pubmed]
  7. The protein kinase ERK3 is encoded by a single functional gene: genomic analysis of the ERK3 gene family. Turgeon, B., Lang, B.F., Meloche, S. Genomics (2002) [Pubmed]
  8. Proteasome- and p38-dependent regulation of ERK3 expression. Zimmermann, J., Lamerant, N., Grossenbacher, R., Furst, P. J. Biol. Chem. (2001) [Pubmed]
  9. Nuclear export of ERK3 by a CRM1-dependent mechanism regulates its inhibitory action on cell cycle progression. Julien, C., Coulombe, P., Meloche, S. J. Biol. Chem. (2003) [Pubmed]
  10. ERK3 is a constitutively nuclear protein kinase. Cheng, M., Boulton, T.G., Cobb, M.H. J. Biol. Chem. (1996) [Pubmed]
  11. Distribution of ERK1/2 and ERK3 during normal rat fetal lung development. Kling, D.E., Brandon, K.L., Sollinger, C.A., Cavicchio, A.J., Ge, Q., Kinane, T.B., Donahoe, P.K., Schnitzer, J.J. Anat. Embryol. (2006) [Pubmed]
  12. Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer. Liang, B., Wang, S., Zhu, X.G., Yu, Y.X., Cui, Z.R., Yu, Y.Z. World J. Gastroenterol. (2005) [Pubmed]
  13. Regulation of ERK3/MAPK6 expression by BRAF. Hoeflich, K.P., Eby, M.T., Forrest, W.F., Gray, D.C., Tien, J.Y., Stern, H.M., Murray, L.J., Davis, D.P., Modrusan, Z., Seshagiri, S. Int. J. Oncol. (2006) [Pubmed]
  14. Identification of extracellular signal-regulated kinase 3 as a new interaction partner of cyclin D3. Sun, M., Wei, Y., Yao, L., Xie, J., Chen, X., Wang, H., Jiang, J., Gu, J. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
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