Models of the different conformations of p47phox in resting, primed, and activated neutrophils: role of Pin1 and phosphorylation. In resting cells, p47phox is not phosphorylated and has a constrained conformation because of the tight interaction between SH3 domains and the autoinhibitory region (AIR). (1) During priming, p47phox is first phosphorylated by a MAPKinase (ERK1/2 or p38MAPK) on Ser345, and (2) activated Pin1 then binds to this site, (3) inducing the first conformational changes that allow PKC isoforms to phosphorylate p47phox on other sites during activation. (4) Phosphorylation of p47phox on several sites at its C-terminal tail prevents the SH3/AIR interaction, allowing the cryptic SH3 domains to bind to the proline-rich region (PRR) of p22phox (5) and NADPH oxidase hyperactivation.