Novel human homologues of p47 and p67 participate in activation of superoxide-producing NADPH oxidases.

Abstract

PAGE 25238:The image shown in the lower panel on the left of Fig. 3A was not correct. The lower panel on the left (the first from the left) incorrectly duplicated the lower panel on the right (the third from the left). In addition, the panels in Fig. 3A were not oriented correctly. The revised figure includes the correct images in the proper orientation. This correction does not affect the interpretation of the results or the conclusions of this work.

Phosphorylation of Noxo1 at threonine 341 regulates its interaction with Noxa1 and the superoxide‐producing activity of Nox1

“…It is known that Nox1 constitutively produces superoxide in cells coexpressing Noxo1 and Noxa1, and cell stimulation with PMA, a potent activator of PKC, leads to a marked increase in superoxide production . To study the role of PKC in PMA‐induced enhancement of Nox1 activity, we tested the effect of GF109203X, an inhibitor of PKC , on the Nox1‐based oxidase reconstituted in CHO cells . As shown in Fig.…”

“…On the other hand, it has been shown that Nox1‐catalyzed ROS production in vascular smooth muscle cells is enhanced upon stimulation with angiotensin II, platelet‐derived growth factor and enthothelin‐1 . Consistent with these observations, the Nox1‐based oxidase reconstituted in cultured cells can also be further increased in a manner dependent on cell stimulants such as PMA and angiotensin II . However, the mechanism for the stimulus‐induced enhancement of Nox1 activity is not well understood.…”

“…Nox1 is also expressed in vascular smooth muscle cells, but to a lesser extent, and has been shown to be involved in pathological events in the vascular system such as angiotensin II mediated hypertension . Similar to Nox2, Nox1 forms a functional heterodimer with p22 phox . Superoxide production by Nox1 absolutely requires coexpression of the p47 phox homologous organizer Noxo1 (Nox organizer 1) and the p67 phox ‐related protein Noxa1 (Nox activator 1) , whereas Rac is involved in full activation of Nox1 .…”

“…Similar to Nox2, Nox1 forms a functional heterodimer with p22 phox . Superoxide production by Nox1 absolutely requires coexpression of the p47 phox homologous organizer Noxo1 (Nox organizer 1) and the p67 phox ‐related protein Noxa1 (Nox activator 1) , whereas Rac is involved in full activation of Nox1 . In contrast to the Nox2‐based oxidase, whose activity is tightly repressed in the resting state, Nox1 constitutively produces a substantial amount of superoxide in the presence of Noxo1 and Noxa1 .…”

“…Superoxide production by Nox1 absolutely requires coexpression of the p47 phox homologous organizer Noxo1 (Nox organizer 1) and the p67 phox ‐related protein Noxa1 (Nox activator 1) , whereas Rac is involved in full activation of Nox1 . In contrast to the Nox2‐based oxidase, whose activity is tightly repressed in the resting state, Nox1 constitutively produces a substantial amount of superoxide in the presence of Noxo1 and Noxa1 . The constitutive activity is considered to be partially due to stimulus‐independent association of Noxo1 with p22 phox and membrane phospholipids, because of the absence of the AIR in Noxo1 .…”