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Gene Review

MAP3K13  -  mitogen-activated protein kinase kinase...

Homo sapiens

Synonyms: LZK, Leucine zipper-bearing kinase, MEKK13, MLK, Mitogen-activated protein kinase kinase kinase 13, ...
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High impact information on MAP3K13

  • The Drosophila MLK Slipper regulates JNK to control dorsal closure during embryonic morphogenesis [1].
  • Together, these results reveal that peroxynitrite-induced activation of the intrinsic apoptotic pathway involves interactions with the MLK/MAPK and Akt signaling pathways [2].
  • We now report that a single kinase, the mitogen-activated protein kinase kinase kinase dual leucine zipper-bearing kinase (DLK), acts in the epidermis to promote the terminal differentiation of human keratinocytes [3].
  • The LZK cDNA encoded a 966-amino acid polypeptide that contains a kinase catalytic domain and double leucine/isoleucine zippers separated by a short spacer region [4].
  • The recombinant LZK autophosphorylated in the presence of ATP and divalent cations, and exhibited serine/threonine kinase catalytic activity [4].

Biological context of MAP3K13

  • Expression of LZK in COS7 cells induced phosphorylation of c-Jun and activation of JNK-1, indicating the association of LZK in the c-Jun amino-terminal kinase/stress-activated protein kinase pathway [4].
  • The amino acid sequence of the kinase catalytic domain was a hybrid between those in serine/threonine and tyrosine protein kinases, indicating that LZK belongs to the subfamily of the mixed lineage kinase (MLK) family [4].
  • We previously cloned a cDNA encoding LZK from a human cerebellum cDNA library [5].
  • Polymerase chain-reaction (PCR) studies indicated that the human LZK coding sequence is composed of 13 exons, and that all the splice acceptor and donor sequences obey the GT-AG rule [5].
  • Differences in BG resistance, activity, and stability between P140K, MLK, and G156A suggest that P140K may be the optimal mutant for drug resistance gene transfer [6].

Anatomical context of MAP3K13

  • Northern blot analysis revealed that LZK is expressed most strongly in the pancreas, with a pattern that differs from other MLKs [4].
  • To address this hypothesis, we measured BG + BCNU and BG + TMZ resistance in G156A, P140K, or P138M/V139L/P140K (MLK) MGMT-transduced K562 cells [6].

Associations of MAP3K13 with chemical compounds

  • The results show that higher recovery rates of CT, MKL, and MLK are yielded from RMR powder by extracting with 95% ethanol (10 mL) at 60 degrees C for 30 min [7].

Physical interactions of MAP3K13

  • We also provided evidence that LZK was associated directly with the IKK complex through the kinase domain, and that AOP-1 was recruited to the IKK complex through the binding to LZK [8].

Regulatory relationships of MAP3K13

  • Using similar assay systems, we demonstrated that LZK activated NF-kappaB-dependent transcription through IKK activation only weakly, but this was reproducible, and that AOP-1 enhanced the LZK-induced NF-kappaB activation [8].

Other interactions of MAP3K13

  • We also identify the C-terminal functional region of LZK, which is indispensable for the activation of SEK1, but not that of MKK7 [9].
  • Consistent with this hypothesis, we provided evidence that LZK is associated with the C-terminal region of JIP-1 through its kinase catalytic domain [10].

Analytical, diagnostic and therapeutic context of MAP3K13

  • However, hematopoietic K562 cells transduced with MFG-G156A, P140K, or MLK had similar degrees of BG and BCNU as well as BG and TMZ resistance when treated with concentrations of BG (< or =25 microM) achieved in clinical trials, suggesting similar efficacy in many in vivo applications [6].


  1. Mixed-lineage kinase control of JNK and p38 MAPK pathways. Gallo, K.A., Johnson, G.L. Nat. Rev. Mol. Cell Biol. (2002) [Pubmed]
  2. Two distinct signaling pathways regulate peroxynitrite-induced apoptosis in PC12 cells. Shacka, J.J., Sahawneh, M.A., Gonzalez, J.D., Ye, Y.Z., D'Alessandro, T.L., Estévez, A.G. Cell Death Differ. (2006) [Pubmed]
  3. The mitogen-activated protein kinase kinase kinase dual leucine zipper-bearing kinase (DLK) acts as a key regulator of keratinocyte terminal differentiation. Robitaille, H., Proulx, R., Robitaille, K., Blouin, R., Germain, L. J. Biol. Chem. (2005) [Pubmed]
  4. Molecular cloning and functional expression of a cDNA encoding a new member of mixed lineage protein kinase from human brain. Sakuma, H., Ikeda, A., Oka, S., Kozutsumi, Y., Zanetta, J.P., Kawasaki, T. J. Biol. Chem. (1997) [Pubmed]
  5. Genomic organization and fine-mapping of the human leucine zipper-bearing kinase (LZK) gene. Ikeda, A., Sakuma, H., Masaki, M., Kozutsumi, Y., Oka, S., Inazawa, J., Kawasaki, T. J. Biochem. Mol. Biol. Biophys. (2002) [Pubmed]
  6. Characterization of the P140K, PVP(138-140)MLK, and G156A O6-methylguanine-DNA methyltransferase mutants: implications for drug resistance gene therapy. Davis, B.M., Roth, J.C., Liu, L., Xu-Welliver, M., Pegg, A.E., Gerson, S.L. Hum. Gene Ther. (1999) [Pubmed]
  7. Synchronous analysis method for detection of citrinin and the lactone and acid forms of monacolin K in red mold rice. Lee, C.L., Wang, J.J., Pan, T.M. Journal of AOAC International. (2006) [Pubmed]
  8. Mixed lineage kinase LZK and antioxidant protein-1 activate NF-kappaB synergistically. Masaki, M., Ikeda, A., Shiraki, E., Oka, S., Kawasaki, T. Eur. J. Biochem. (2003) [Pubmed]
  9. Identification and characterization of functional domains in a mixed lineage kinase LZK. Ikeda, A., Masaki, M., Kozutsumi, Y., Oka, S., Kawasaki, T. FEBS Lett. (2001) [Pubmed]
  10. Mixed lineage kinase LZK forms a functional signaling complex with JIP-1, a scaffold protein of the c-Jun NH(2)-terminal kinase pathway. Ikeda, A., Hasegawa, K., Masaki, M., Moriguchi, T., Nishida, E., Kozutsumi, Y., Oka, S., Kawasaki, T. J. Biochem. (2001) [Pubmed]
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