Cargando…

Phosphorylation of threonine 154 in p40(phox) is an important physiological signal for activation of the neutrophil NADPH oxidase

The neutrophil nicotinamide adenine dinucleotide phosphate-oxidase is a multisubunit enzyme (comprising gp91(phox), p22(phox), p67(phox), p40(phox), p47(phox), and Rac) that plays a vital role in microbial killing. The recent discovery of a chronic granulomatous disease patient who expresses a mutan...

Descripción completa

Detalles Bibliográficos
Autores principales: Chessa, Tamara A. M., Anderson, Karen E., Hu, Yanhua, Xu, Qingbo, Rausch, Oliver, Stephens, Len R., Hawkins, Phillip T.
Formato: Texto
Lenguaje:English
Publicado: American Society of Hematology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031388/
https://www.ncbi.nlm.nih.gov/pubmed/20861461
http://dx.doi.org/10.1182/blood-2010-08-300889
_version_ 1782197342937546752
author Chessa, Tamara A. M.
Anderson, Karen E.
Hu, Yanhua
Xu, Qingbo
Rausch, Oliver
Stephens, Len R.
Hawkins, Phillip T.
author_facet Chessa, Tamara A. M.
Anderson, Karen E.
Hu, Yanhua
Xu, Qingbo
Rausch, Oliver
Stephens, Len R.
Hawkins, Phillip T.
author_sort Chessa, Tamara A. M.
collection PubMed
description The neutrophil nicotinamide adenine dinucleotide phosphate-oxidase is a multisubunit enzyme (comprising gp91(phox), p22(phox), p67(phox), p40(phox), p47(phox), and Rac) that plays a vital role in microbial killing. The recent discovery of a chronic granulomatous disease patient who expresses a mutant p40(phox) subunit, together with the development of mouse models of p40(phox) function, indicate phosphatidylinositol 3-phosphate binding to the PX domain of p40(phox) is an important signal for oxidase activation. However, the presence of other conserved residues and domains in p40(phox) suggest further regulatory roles for this protein. To test this, we introduced wild-type and mutated versions of p40(phox) into fully differentiated mouse neutrophils by retroviral transduction of p40(phox)(−/−) bone marrow progenitors and repopulation of the bone marrow compartment in radiation chimaeras. Phosphorylation of p40(phox) on threonine 154, but not serine 315, was required for full oxidase activation in response to formylated bacterial peptide fMLP, serum-opsonized S aureus, and immunoglobulin-opsonized sheep red blood cells. A functional SH3 domain was not required for oxidase activation, and deletion of the entire domain resulted in enhanced oxidase responses. Phosphorylation of threonine 154 in response to S aureus was mediated by protein kinase Cδ and was required for full translocation of p47(phox) to phagosomes. These results define an important new element in the physiological activation of the oxidase.
format Text
id pubmed-3031388
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher American Society of Hematology
record_format MEDLINE/PubMed
spelling pubmed-30313882011-03-03 Phosphorylation of threonine 154 in p40(phox) is an important physiological signal for activation of the neutrophil NADPH oxidase Chessa, Tamara A. M. Anderson, Karen E. Hu, Yanhua Xu, Qingbo Rausch, Oliver Stephens, Len R. Hawkins, Phillip T. Blood Phagocytes, Granulocytes, and Myelopoiesis The neutrophil nicotinamide adenine dinucleotide phosphate-oxidase is a multisubunit enzyme (comprising gp91(phox), p22(phox), p67(phox), p40(phox), p47(phox), and Rac) that plays a vital role in microbial killing. The recent discovery of a chronic granulomatous disease patient who expresses a mutant p40(phox) subunit, together with the development of mouse models of p40(phox) function, indicate phosphatidylinositol 3-phosphate binding to the PX domain of p40(phox) is an important signal for oxidase activation. However, the presence of other conserved residues and domains in p40(phox) suggest further regulatory roles for this protein. To test this, we introduced wild-type and mutated versions of p40(phox) into fully differentiated mouse neutrophils by retroviral transduction of p40(phox)(−/−) bone marrow progenitors and repopulation of the bone marrow compartment in radiation chimaeras. Phosphorylation of p40(phox) on threonine 154, but not serine 315, was required for full oxidase activation in response to formylated bacterial peptide fMLP, serum-opsonized S aureus, and immunoglobulin-opsonized sheep red blood cells. A functional SH3 domain was not required for oxidase activation, and deletion of the entire domain resulted in enhanced oxidase responses. Phosphorylation of threonine 154 in response to S aureus was mediated by protein kinase Cδ and was required for full translocation of p47(phox) to phagosomes. These results define an important new element in the physiological activation of the oxidase. American Society of Hematology 2010-12-23 /pmc/articles/PMC3031388/ /pubmed/20861461 http://dx.doi.org/10.1182/blood-2010-08-300889 Text en © 2010 by The American Society of Hematology https://creativecommons.org/licenses/by-nc/3.0/us/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/us/ (https://creativecommons.org/licenses/by-nc/3.0/us/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Phagocytes, Granulocytes, and Myelopoiesis
Chessa, Tamara A. M.
Anderson, Karen E.
Hu, Yanhua
Xu, Qingbo
Rausch, Oliver
Stephens, Len R.
Hawkins, Phillip T.
Phosphorylation of threonine 154 in p40(phox) is an important physiological signal for activation of the neutrophil NADPH oxidase
title Phosphorylation of threonine 154 in p40(phox) is an important physiological signal for activation of the neutrophil NADPH oxidase
title_full Phosphorylation of threonine 154 in p40(phox) is an important physiological signal for activation of the neutrophil NADPH oxidase
title_fullStr Phosphorylation of threonine 154 in p40(phox) is an important physiological signal for activation of the neutrophil NADPH oxidase
title_full_unstemmed Phosphorylation of threonine 154 in p40(phox) is an important physiological signal for activation of the neutrophil NADPH oxidase
title_short Phosphorylation of threonine 154 in p40(phox) is an important physiological signal for activation of the neutrophil NADPH oxidase
title_sort phosphorylation of threonine 154 in p40(phox) is an important physiological signal for activation of the neutrophil nadph oxidase
topic Phagocytes, Granulocytes, and Myelopoiesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031388/
https://www.ncbi.nlm.nih.gov/pubmed/20861461
http://dx.doi.org/10.1182/blood-2010-08-300889
work_keys_str_mv AT chessatamaraam phosphorylationofthreonine154inp40phoxisanimportantphysiologicalsignalforactivationoftheneutrophilnadphoxidase
AT andersonkarene phosphorylationofthreonine154inp40phoxisanimportantphysiologicalsignalforactivationoftheneutrophilnadphoxidase
AT huyanhua phosphorylationofthreonine154inp40phoxisanimportantphysiologicalsignalforactivationoftheneutrophilnadphoxidase
AT xuqingbo phosphorylationofthreonine154inp40phoxisanimportantphysiologicalsignalforactivationoftheneutrophilnadphoxidase
AT rauscholiver phosphorylationofthreonine154inp40phoxisanimportantphysiologicalsignalforactivationoftheneutrophilnadphoxidase
AT stephenslenr phosphorylationofthreonine154inp40phoxisanimportantphysiologicalsignalforactivationoftheneutrophilnadphoxidase
AT hawkinsphillipt phosphorylationofthreonine154inp40phoxisanimportantphysiologicalsignalforactivationoftheneutrophilnadphoxidase