Role for the first SH3 domain of p67phox in activation of superoxide-producing NADPH oxidases

摘要: Abstract The membrane-bound NADPH oxidase in phagocytes, gp91phox (a.k.a. Nox2), produces superoxide, a precursor of microbicidal oxidants, thereby playing crucial role host defense. Activation gp91phox/Nox2 requires assembly with the cytosolic proteins p67phox and p47phox, each containing two SH3 domains. Although C-terminal domain is responsible for binding to little known about first (N-terminal) [SH3(N)]. Here we show that truncation p67phox-SH3(N), but not substitution arginine invariant residue Trp-277 SH3(N), results an impaired activation gp91phox/Nox2. impairment overcome by higher expression SH3(N)-defective cells, suggesting SH3(N) primarily increases affinity complex. On other hand, p67phox-SH3(N) involved Nox1 Nox3, closely-related homologues Thus specifically functions probably via facilitating assembly.