background:
Mixed lineage kinases are a family of protein kinases sharing two leucine zipper-like motifs, which are known to mediate protein dimerization, and a kinase domain whose primary structure is similar to both the tyrosine-specific and the serine/threonine-specific kinase classes. Members of the mixed-lineage kinase (MLK) family include MLK1, MLK2, MLK3 and dual leucine zipper kinase, also designated DLK. MLKs are expressed in neuronal cells where they are likely to interact between Rac1/Cdc42, MKK4 and MKK7 in death signaling. The human MLK1 gene maps to chromosome 14q24.3-q31 and is expressed in epithelial tumor cell lines of the colon, breast, and esophagus. The human MLK2 gene maps to chromosome 19 q13.2. and encodes a predicted 954 amino acid, src homology 3 (SH3) domain-containing protein. The human MLK3 gene maps to chromosome 11q13.1-13.3 and encodes a 847 amino acid, SH3 domain- and proline rich region-containing protein. Apoptosis mechanisms rely on MLKs as an upstream intermediate of mitochondrial cytochrome c release and caspase activation.
Function:
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade through the phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The MKK/JNK signaling pathway regulates stress response via activator protein-1 (JUN) and GATA4 transcription factors. Plays also a role in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.
Subunit:
Homodimer.
Tissue Specificity:
Expressed in epithelial tumor cell lines of colonic, breast and esophageal origin.
Post-translational modifications:
Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation. Thr-312 is likely to be the main autophosphorylation site. Autophosphorylation also occurs on Thr-304 and Ser-308.
DISEASE:
Note=May play a role in esophageal cancer susceptibility and/or development.
Similarity:
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Contains 1 protein kinase domain.
Contains 1 SH3 domain.
Database links:
Entrez Gene: 4293 Human
Entrez Gene: 338372 Mouse
Entrez Gene: 500690 Rat
Omim: 600136 Human
SwissProt: P80192 Human
SwissProt: Q3U1V8 Mouse
Unigene: 445496 Human
Unigene: 593542 Human
Unigene: 35284 Mouse
Unigene: 18168 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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