<p>This entry represents mitogen-activated protein kinase kinase kinase, types 12/13 (MAP3K12 and MAP3K13), which form part of the mixed lineage kinase (MLK) family. </p><p>MAP3K12 (also known as leucine-zipper protein kinase (ZPK), dual leucine zipper-bearing kinase (DLK) or MAPK-upstream kinase (MUK)) is a MAPKKK class protein kinase that induces JNK/SAPK activation. MAP3K12 is known to interact with MUK-binding inhibitory protein (MBIP). MBIP contains two tandem leucine-zipper-like motifs; MBIP interacts with one of the two leucine-zipper-like motifs of MAP3K12 and inhibits the activity of MAP3K12 to induce JNK/SAPK activation [<cite idref="PUB00044665"/>, <cite idref="PUB00044666"/>]. MAP3K12 is autophosphorylated on Ser/Thr in cytosol under basal conditions, and dephosphorylated when membrane-associated.</p><p>MAP3K13 (also known as leucine zipper-bearing kinase LZK) activates the c-Jun-NH2 terminal kinase (JNK) pathway through activation of the MAP kinase kinase MAP2K7 [<cite idref="PUB00044667"/>]. MAP3K13 acts synergistically with peroxiredoxin-3 (PRDX3) to regulate the activation of NF-kappa-B in the cytosol. This activation is kinase-dependent and involves activating the IKK complex, the IKBKB-containing complex that phosphorylates inhibitors of NF-kappa-B [<cite idref="PUB00044667"/>].</p>