Sunday, August 9, 2009

DLK the master of biological processes


Dual leucine zipper-bearing kinase (DLK) is a member of the mixed-lineage kinase (MLK) subfamily of serine/threonine kinases, an important upstream component of the mitogen-activated protein kinase (MAPK) pathways. The DLK gene is expressed in a tissue-specific manner and its targeted deletion in mice causes perinatal death with defects in brain development. Recent analyses of mice, flies and worms bearing loss-of-functions mutations in either DLK or its invertebrate orthologs also demonstrated that this enzyme has a central role in the neuronal response to injury, being required for axon regeneration or degeneration depending on the species. Additionally, using overexpression and knockdown approaches, it was shown that DLK has pro-differentiation and pro-apoptotic effects in mammalian cells. Although little is known about how DLK is activated and modulated, accumulating evidence suggests a complex regulation that involves phosphorylation, interactions with different protein partners and ubiquitin-mediated degradation. Thus, DLK seems to be a key regulator for various fundamental biological processes, although the precise molecular mechanisms by which it mediates such effects remain to be determined.

Alternative names for this molecule: DLK; Dual leucine zipper bearing kinase; Dual leucine zipper-bearing kinase; MAP kinase upstream kinase; Map3k12; Mitogen activated protein kinase kinase kinase 12; Mitogen-activated protein kinase kinase kinase 12; MUK; Zipper protein kinase; ZPK

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