The membrane-bound NADPH oxidase in phagocytes, gp91phox (a.k.a. Nox2), produces superoxide, a precursor of microbicidal oxidants, thereby playing a crucial role in host defense. Activation of gp91phox/Nox2 requires assembly with the cytosolic proteins p67phox and p47phox, each containing two SH3 domains. Although the C-terminal SH3 domain of p67phox is responsible for binding to p47phox, little is known about the role for the first (N-terminal) SH3 domain [SH3(N)]. Here we show that truncation of p67phox-SH3(N), but not substitution of arginine for the invariant residue Trp-277 in SH3(N), results in an impaired activation of gp91phox/Nox2. The impairment is overcome by higher expression of an SH3(N)-defective p67phox in cells, suggesting that SH3(N) primarily increases the affinity of p67phox for the oxidase complex. On the other hand, p67phox-SH3(N) is not involved in activation of Nox1 and Nox3, closely-related homologues of gp91phox/Nox2. Thus p67phox-SH3(N) specifically functions in gp91phox/Nox2 activation probably via facilitating oxidase assembly.
|Number of pages||5|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - Feb 6 2009|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology