The PX Domain as a Novel Phosphoinositide- Binding Module

Ago, Tetsuro; Takeya, Ryu; Hiroaki, Hidekazu; Kuribayashi, Futoshi; Ito, Takashi; Kohda, Daisuke; Sumimoto, Hideki

doi:10.1006/bbrc.2001.5629

Cited by 97 publications

(97 citation statements)

References 25 publications

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“…Two recent studies [204,205] have further confirmed the conclusion that the PX domain is a PI-interacting motif. The crystal structure of the p40 phox PX domain bound to PtdIns3P has been resolved, revealing that the PX domain embraces the 3-phosphate of PtdIns3P with a positively charged pocket [206].…”

Section: Note Added In Proof (Received 8 November 2001)mentioning

confidence: 68%

The Phox homology (PX) domain, a new player in phosphoinositide signalling

Seet

Hanson

et al. 2001

Biochemical Journal

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Phosphoinositides are key regulators of diverse cellular processes. The pleckstrin homology (PH) domain mediates the action of PtdIns(3,4)P # , PtdIns(4,5)P # and PtdIns(3,4,5)P $ , while the FYVE domain relays the pulse of PtdIns3P. The recent establishment that the Phox homology (PX) domain interacts with PtdIns3P and other phosphoinositides suggests another mechanism by which phosphoinositides can regulate\integrate multiple cellular events via a spectrum of PX domain-containing proteins.

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Section: Note Added In Proof (Received 8 November 2001)mentioning

confidence: 68%

The Phox homology (PX) domain, a new player in phosphoinositide signalling

Seet

Hanson

et al. 2001

Biochemical Journal

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“…p40phox binds to p67phox via the Phox and Bem1 (PBI) domains (Nakamura et al, 1998;Ago et al, 2001;Noda et al, 2003) and with plasma membrane phosphoinositides via its PX domain (Ellson et al, 2001;Honbou et al, 2007;Bissonnette et al, 2008), analogous to p47phox. X-ray crystallography and nuclear magnetic resonance predict that p67phox serves as a link between p47phox and p40phox by interacting with both of these regulatory subunits.…”

Section: Molecular Description Of Nadph Oxidasesmentioning

confidence: 99%

NADPH Oxidases as Novel Pharmacologic Targets against Influenza A Virus Infection

Vlahos¹,

Selemidis²

2014

Mol Pharmacol

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Influenza A viruses represent a major global health care challenge, with imminent pandemics, emerging antiviral resistance, and long lag times for vaccine development, raising a pressing need for novel pharmacologic strategies that ideally target the pathology irrespective of the infecting strain. Reactive oxygen species (ROS) pervade all facets of cell biology with both detrimental and protective properties. Indeed, there is compelling evidence that activation of the NADPH oxidase 2 (NOX2) isoform of the NADPH oxidase family of ROS-producing enzymes promotes lung oxidative stress, inflammation, injury, and dysfunction resulting from influenza A viruses of low to high pathogenicity, as well as impeding virus clearance. By contrast, the dual oxidase isoforms produce ROS that provide vital protective antiviral effects for the host. In this review, we propose that inhibitors of NOX2 are better alternatives than broad-spectrum antioxidant approaches for treatment of influenza pathologies, for which clinical efficacy may have been limited owing to poor bioavailability and inadvertent removal of beneficial ROS. Finally, we briefly describe the current suite of NADPH oxidase inhibitors and the molecular features of the NADPH oxidase enzymes that could be exploited by drug discovery for development of more specific and novel inhibitors to prevent or treat disease caused by influenza.

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“…The PX domain of p47 phox contains a proline-rich sequence that appears to participate in intradomain binding to the C-SH3 domain of p47 phox (22,26). Moreover, PX domains function as binding sites for phosphatidylinositol phosphates (25,27,29,40). The internal interactions within p47 phox mask the binding to lipids, preventing membrane association.…”

Section: Figmentioning

confidence: 99%

“…The latter, in addition to forming a heterodimer with gp91 phox (23,24), provides a proline-rich binding site for the p47 phox bis-SH3 domain. p47 phox also contains a lipid binding domain (the PX domain) with specificity for 3-phosphorylated lipids, the products of phosphatidylinositol 3-kinase (25)(26)(27)(28)(29). The latter is activated in cells exposed to bacterial products or immune mediators, as are the kinases that phosphorylate p47 phox itself.…”

mentioning

confidence: 99%