Functional modules and expression of mouse p40phox and p67phox, SH3-domain-containing proteins -: Involved in the phagocyte NADPH oxidase complex

The phagocyte NADPH oxidase is activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. The formation of the active oxidase complex at the membrane requires translocation of the Rac GTPase and two specialized cytosolic proteins that harbor SH3 domains, p67(phox) and p47(phox). Another SH3-domain-containing protein p40(phox), which is constitutively associated with p67(phox) in phagocytes, also enters the complex upon cell stimulation. Here we describe how we cloned mouse cDNAs encoding p40(phox) and its partner in phagocytes, p67(phox). Both p40(phox) and p67(phox) comprise several protein-binding modules that are structurally and functional well conserved between mouse and human, indicating their nature as adaptor proteins. We have also systematically investigated expression of the gene for p40(phox) in comparison with those for p67(phox) and p47(phox). Distributions of the mRNAs for the three proteins among tissues are similar, with the most abundant: expression in the spleen. The messages are abundant not only in phagocytic cells, but also in B cell lineage. The p40(phox) gene, but not the other two, is expressed in some types of cells such as plasma cells and T lymphocytes, Furthermore, in situ hybridization analysis shows that the p40(phox) mRNA is distributed in neuronal cells of mouse brain, providing evidence that one of the genes for the specialized oxidase factors is expressed in neurons. These observations raise the possibility that the adaptor protein p40(phox) plays a heretofore unsuspected role via interacting with other proteins in the cells that do not express p67(phox)or p47(phox).