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Gene Review

MEK1  -  Mek1p

Saccharomyces cerevisiae S288c

Synonyms: MRE4, Meiosis-specific serine/threonine-protein kinase MEK1, O6357, YOR351C
 
 
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Disease relevance of MEK1

  • We found that the type II transcriptional response to IFN-gamma could be suppressed by inhibition of MEK1/2 kinase activity by MEK1/2 inhibitor U0126 in the hepatoma cell line Huh-7 [1].
 

High impact information on MEK1

  • In mutants that undergo checkpoint-mediated pachytene arrest, Mek1 is active and Red1 remains phosphorylated [2].
  • Activation of Mek1 requires the initiation of meiotic recombination and certain DNA damage checkpoint proteins [2].
  • Mek1 kinase activity and checkpoint-induced pachytene arrest are counteracted by protein phosphatase type 1 (Glc7) [2].
  • Pachytene exit controlled by reversal of Mek1-dependent phosphorylation [2].
  • Intracellular signaling from receptor tyrosine kinases in mammalian cells results in activation of a signal cascade that includes the guanine nucleotide-binding protein Ras and the protein kinases Raf, MEK [mitogen-activated protein kinase (MAPK) or extracellular signal-regulated kinase (ERK) kinase], and MAPK [3].
 

Biological context of MEK1

  • A third meiosis-specific gene, MEK1, which encodes a putative serine/threonine protein kinase, is also important for proper AE function, suggesting that AE formation is regulated by phosphorylation [4].
  • Red1p, a MEK1-dependent phosphoprotein that physically interacts with Hop1p during meiosis in yeast [4].
  • We report here the effects of mutations in two other (meiosis-specific) genes, RED1 and MEK1/MRE4, that encode a chromosome structure component and a protein kinase, respectively [5].
  • Partner choice during meiosis is regulated by Hop1-promoted dimerization of Mek1 [6].
  • This change in partner choice is due in part to a barrier to sister chromatid repair (BSCR) created by the meiosis-specific kinase, Mek1, in a complex with two other meiosis-specific proteins, Hop1 and Red1 [6].
 

Anatomical context of MEK1

  • A mutant rat cell clone that suppresses the transformation defects of RAS effector loop substitutions is heterozygous for mutations in c-raf1 and MEK1 [7].
  • In oocytes treated with the MEK1 inhibitor U0126, the MAPK pathway does not become activated, and Bub1 remains in its low-activity, unshifted form [8].
  • Mkh1, a MEK kinase required for cell wall integrity and proper response to osmotic and temperature stress in Schizosaccharomyces pombe [9].
  • The MEK kinase Ssk2p promotes actin cytoskeleton recovery after osmotic stress [10].
 

Associations of MEK1 with chemical compounds

  • Examination of the roles of downstream checkpoint kinases reveals that Cds1, but not Chk1 or Mek1, is required for suppression of DSB in the presence of hydroxyurea [11].
 

Regulatory relationships of MEK1

  • Co-immunoprecipitation experiments demonstrated that the interaction between Hop1p and Red1p is enhanced by the presence of MEK1 [4].
  • The mre4 spore lethality can be suppressed by spo13, a mutation that causes cells to bypass the reductional division [12].
 

Other interactions of MEK1

  • Thus, MEK1-dependent phosphorylation of Red1p facilitates the formation of Hop1p/Red1p hetero-oligomers, thereby enabling the formation of functional AEs [4].
  • Experiments using mek1-as1 demonstrate that the requirement for Mek1 kinase activity coincides with the formation of double strand breaks (DSBs) and that this activity is necessary after DSB formation to prevent repair by DMC1-independent pathways [13].
  • The MRE4 gene encodes a novel protein kinase homologue required for meiotic recombination in Saccharomyces cerevisiae [12].
  • Overproduction of either the meiotic chromosomal protein Red1 or the meiotic kinase Mek1 bypasses this checkpoint, allowing zip1 cells to sporulate [14].
  • Diploids homozygous for a mek1 null mutation produce only 13% viable spores. mek1 spore inviability is rescued by a spo13 mutation, which causes cells to bypass the meiosis I division [15].
 

Analytical, diagnostic and therapeutic context of MEK1

References

  1. Mechanistic link between the anti-HCV effect of interferon gamma and control of viral replication by a Ras-MAPK signaling cascade. Huang, Y., Chen, X.C., Konduri, M., Fomina, N., Lu, J., Jin, L., Kolykhalov, A., Tan, S.L. Hepatology (2006) [Pubmed]
  2. Pachytene exit controlled by reversal of Mek1-dependent phosphorylation. Bailis, J.M., Roeder, G.S. Cell (2000) [Pubmed]
  3. Stimulatory effects of yeast and mammalian 14-3-3 proteins on the Raf protein kinase. Irie, K., Gotoh, Y., Yashar, B.M., Errede, B., Nishida, E., Matsumoto, K. Science (1994) [Pubmed]
  4. Red1p, a MEK1-dependent phosphoprotein that physically interacts with Hop1p during meiosis in yeast. de los Santos, T., Hollingsworth, N.M. J. Biol. Chem. (1999) [Pubmed]
  5. Meiotic cells monitor the status of the interhomolog recombination complex. Xu, L., Weiner, B.M., Kleckner, N. Genes Dev. (1997) [Pubmed]
  6. Partner choice during meiosis is regulated by Hop1-promoted dimerization of Mek1. Niu, H., Wan, L., Baumgartner, B., Schaefer, D., Loidl, J., Hollingsworth, N.M. Mol. Biol. Cell (2005) [Pubmed]
  7. RAS signalling is abnormal in a c-raf1 MEK1 double mutant. Bottorff, D., Stang, S., Agellon, S., Stone, J.C. Mol. Cell. Biol. (1995) [Pubmed]
  8. Bub1 is activated by the protein kinase p90(Rsk) during Xenopus oocyte maturation. Schwab, M.S., Roberts, B.T., Gross, S.D., Tunquist, B.J., Taieb, F.E., Lewellyn, A.L., Maller, J.L. Curr. Biol. (2001) [Pubmed]
  9. Mkh1, a MEK kinase required for cell wall integrity and proper response to osmotic and temperature stress in Schizosaccharomyces pombe. Sengar, A.S., Markley, N.A., Marini, N.J., Young, D. Mol. Cell. Biol. (1997) [Pubmed]
  10. The MEK kinase Ssk2p promotes actin cytoskeleton recovery after osmotic stress. Yuzyuk, T., Foehr, M., Amberg, D.C. Mol. Biol. Cell (2002) [Pubmed]
  11. Rad3-Cds1 mediates coupling of initiation of meiotic recombination with DNA replication. Mei4-dependent transcription as a potential target of meiotic checkpoint. Ogino, K., Masai, H. J. Biol. Chem. (2006) [Pubmed]
  12. The MRE4 gene encodes a novel protein kinase homologue required for meiotic recombination in Saccharomyces cerevisiae. Leem, S.H., Ogawa, H. Nucleic Acids Res. (1992) [Pubmed]
  13. Mek1 kinase activity functions downstream of RED1 in the regulation of meiotic double strand break repair in budding yeast. Wan, L., de los Santos, T., Zhang, C., Shokat, K., Hollingsworth, N.M. Mol. Biol. Cell (2004) [Pubmed]
  14. Bypass of a meiotic checkpoint by overproduction of meiotic chromosomal proteins. Bailis, J.M., Smith, A.V., Roeder, G.S. Mol. Cell. Biol. (2000) [Pubmed]
  15. A meiosis-specific protein kinase homolog required for chromosome synapsis and recombination. Rockmill, B., Roeder, G.S. Genes Dev. (1991) [Pubmed]
  16. Synaptonemal complex morphogenesis and sister-chromatid cohesion require Mek1-dependent phosphorylation of a meiotic chromosomal protein. Bailis, J.M., Roeder, G.S. Genes Dev. (1998) [Pubmed]
 
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