Neutrophils play a crucial role in host defense against microbial infections. During phagocytosis of invading bacteria or fungi, the phagocyte NADPH oxidase produces superoxide. The importance of the oxidase is exemplified by the genetic disorder known as chronic granulomatous disease (CGD). The neutrophils of CGD patients cannot produce superoxide, with the result that affected infants and chi...

Significant evidence has now been accumulated that microglial cells play a central role in the degeneration of DA neurons in animal models of PD. The oxidative stress response by microglial cells, most notably the activity of the enzyme NADPH oxidase, appears to play a central role in the pathology of PD. This oxidative stress response occurs in microglia through the activation of the ERK signa...

The multi-subunit NADPH oxidase complex plays a crucial role in host defense against microbial infection through the production of reactive oxygen species. Activation of the NADPH oxidase requires the targeting of a cytoplasmic p40-p47-p67(phox) complex to the membrane bound heterodimeric p22-gp91(phox) flavocytochrome. This interaction is prevented in the resting state due to an auto-inhibited...

We have isolated mutations in the gene Drosophila methionine aminopeptidase 2 (DMAP2), which encodes a homolog of the type 2 methionine aminopeptidase from yeast, also known as the eukaryotic initiation factor 2alpha (eIF2alpha) associated protein p67. Weak DMAP2 mutations cause ommatidial rotation defects and loss of ventral tissue in the compound eye as well as extra wing veins, whereas stron...

Activation of the phagocyte NADPH oxidase complex requires assembly of the cytosolic factors p47PHOX, p67PHOX, p40PHOX, and Rac with the membrane-bound cytochrome b558. We recently established a direct interaction between p67PHOX and cytochrome b558. In the present study, we show that removal of the C-terminal domain of p67PHOX increased its binding to cytochrome b558. Whereas phosphorylated p4...