P40(PHOX), A 3RD CYTOSOLIC COMPONENT OF THE ACTIVATION COMPLEX OF THENADPH OXIDASE TO CONTAIN SRC HOMOLOGY 3 DOMAINS

The NADPH oxidase generates superoxide in phagocytic cells. It is impo rtant for immunity and its deficiency leads to chronic granulomatous d isease (CGD). It consists of a membrane-bound flavocytochrome b that l ies dormant until activated by the translocation to the plasma membran e of cytosolic proteins, p47phox (phox for phagocyte oxidase), p67phox and p21rac, a small GTP-binding protein. We show here that a novel co mponent, p40phox, forms an activation complex with p47phox and p67phox with which it translocates to the membrane to associate with the flav ocytochrome b. cDNA cloning and amino acid analysis revealed that p40p hox has an src homology 3 (SH3) domain and a large region of sequence similarity with the N-terminus of p47phox. The primary association of p40phox appears to be with p67Pphox, and it is present in reduced amou nts in patients with CGD lacking p67phox.