We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

PtdIns3P binding to the PX domain of p40phox is a physiological signal in NADPH oxidase activation.

The EMBO journal | Oct 4, 2006

The production of reactive oxygen species by the NADPH oxidase complex of phagocytes plays a critical role in our defence against bacterial and fungal infections. The PX domains of two oxidase components, p47(phox) and p40(phox), are known to bind phosphoinositide products of PI3Ks but the physiological roles of these interactions are unclear. We have created mice which carry an R58A mutation in the PX domain of their p40(phox) gene, which selectively prevents binding to PtdIns3P. p40(phoxR58A/R58A) embryos do not develop normally but p40(phoxR58A/-) mice are viable and neutrophils from these animals exhibit significantly reduced oxidase responses compared to those from their p40(phox+/-) siblings (e.g. 60% reduced in response to phagocytosis of Staphylococcus aureus). Wortmannin inhibition of the S. aureus oxidase response correlates with inhibition of phagosomal PtdIns3P accumulation and overlaps with the reduction in this response caused by the R58A mutation, suggesting PI3K regulation of this response is substantially dependent on PtdIns3P-binding to p40(phox). p40(phoxR58A/-) mice are significantly compromised in their ability to kill S. aureus in vivo, defining the physiological importance of this interaction.

Pubmed ID: 16990793 RIS Download

Mesh terms: Amino Acid Sequence | Androstadienes | Animals | Cells, Cultured | Enzyme Activation | Immunoglobulin G | Mice | Mice, Mutant Strains | Microspheres | Molecular Sequence Data | N-Formylmethionine Leucyl-Phenylalanine | NADPH Oxidase | Neutrophils | Peritoneum | Phosphatidylinositol Phosphates | Phosphoproteins | Protein Structure, Tertiary | Reactive Oxygen Species | Response Elements | Signal Transduction | Staphylococcus aureus | Tetradecanoylphorbol Acetate | Tumor Necrosis Factor-alpha

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: Biotechnology and Biological Sciences Research Council, Id: BBS/B/01979

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.