High impact information on DAPK2

• In addition, expression of the dominant negative mutant of DRP-1 or of DAPk antisense mRNA reduced autophagy induced by antiestrogens, amino acid starvation, or administration of interferon-gamma [1].
• DRP-1 is a pro-apoptotic Ca2+/calmodulin (CaM)-regulated serine/threonine kinase, recently isolated as a novel member of the DAP-kinase family of proteins [2].
• Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by controlling dimerization and calmodulin binding [2].
• In proposed compensatory responses, Lyn-/- erythroblasts expressed increased levels of activated Akt and p60-Src and decreased levels of death-associated protein kinase-2 [3].
• Ectopically expressed DRP-1 induced apoptosis in various types of cells [4].

Biological context of DAPK2

• Overexpression of DAPK2, but not the kinase negative mutant, significantly induced the morphological changes characteristic of apoptosis [5].
• The mapping results indicated that DAPK2 is located in the central region of mouse chromosome 9 [5].
• Treatment of agonists that elevate intracellular Ca2+-concentration led to the activation of DAPK2 and transfection studies revealed that DAPK2 is localized in the cytoplasm [5].
• Also introduced are two new putative negative regulators of Epo-dependent erythropoiesis, DYRK3 and DAPK2 kinases [6].
• Finally, immunogold staining showed that DRP-1 is localized inside the autophagic vesicles, suggesting a direct involvement of this kinase in the process of autophagy [1].

Anatomical context of DAPK2

• DAPK2 mRNA is expressed abundantly in heart, lung and skeletal muscle [5].
• Thus, the dynein/dynactin complex plays an unexpected role in the regulation of mitochondrial morphology in living cells, by controlling the recruitment of Drp1 to these organelles [7].
• Suggesting that an alteration in the balance between mitochondrial fission and fusion may be involved in both of these changes, overexpression of p50 induced the translocation of the fission factor dynamin-related protein (Drp1) from mitochondrial membranes to the cytosol and microsomes [7].
• Recent studies have demonstrated that peroxisome division requires at least one dynamin-like protein, Vps1p, in the yeast Saccharomyces cerevisiae and DLP1 (DRP1) in mammalian cells [8].
• Inhibition of Drp1 by overexpression of a dominant-negative mutant counteracts the conversion to a punctiform mitochondrial phenotype, prevents the loss of the mitochondrial membrane potential and the release of cytochrome c, and reveals a reproducible swelling of the organelles [9].

Associations of DAPK2 with chemical compounds

• DRP-1 is a 42-kDa Ca(2+)/calmodulin (CaM)-regulated serine threonine kinase which shows high degree of homology to DAP kinase [4].

References