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].

References