Phosphatidylinositol 3'-kinase activity is critical for initiating the oxidative burst and bacterial destruction during CEACAM3-mediated phagocytosis.

2.50
HDL Handle:
http://hdl.handle.net/10033/237371
Title:
Phosphatidylinositol 3'-kinase activity is critical for initiating the oxidative burst and bacterial destruction during CEACAM3-mediated phagocytosis.
Authors:
Buntru, Alexander; Kopp, Kathrin; Voges, Maike; Frank, Ronald; Bachmann, Verena; Hauck, Christof R
Abstract:
Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3) is an immunoglobulin-related receptor expressed on human granulocytes. CEACAM3 functions as a single chain phagocytotic receptor recognizing gram-negative bacteria such as Neisseria gonorrhoeae, which possess CEACAM-binding adhesins on their surface. The cytoplasmic domain of CEACAM3 contains an immunoreceptor tyrosine-based activation motif (ITAM)-like sequence that is phosphorylated upon receptor engagement. Here we show that the SH2 domains of the regulatory subunit of phosphatidylinositol 3'-kinase (PI3K) bind to tyrosine residue 230 of CEACAM3 in a phosphorylation-dependent manner. PI3K is rapidly recruited and directly associates with CEACAM3 upon bacterial binding as shown by FRET analysis. Although PI3K activity is not required for efficient uptake of the bacteria by CEACAM3-transfected cells or primary human granulocytes, it is critical for the stimulated production of reactive oxygen species by infected phagocytes and the intracellular degradation of CEACAM-binding bacteria. Together, our results highlight the ability of CEACAM3 to coordinate signaling events that not only mediate bacterial uptake, but also trigger the killing of internalized pathogens.
Affiliation:
Lehrstuhl für Zellbiologie, Universität Konstanz, 78457 Konstanz, Germany.
Citation:
Phosphatidylinositol 3'-kinase activity is critical for initiating the oxidative burst and bacterial destruction during CEACAM3-mediated phagocytosis. 2011, 286 (11):9555-66 J. Biol. Chem.
Journal:
The Journal of biological chemistry
Issue Date:
18-Mar-2011
URI:
http://hdl.handle.net/10033/237371
DOI:
10.1074/jbc.M110.216085
PubMed ID:
21216968
Type:
Article
Language:
en
ISSN:
1083-351X
Appears in Collections:
Publications of Dept. Chemical Biology (CBIO)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorBuntru, Alexanderen_GB
dc.contributor.authorKopp, Kathrinen_GB
dc.contributor.authorVoges, Maikeen_GB
dc.contributor.authorFrank, Ronalden_GB
dc.contributor.authorBachmann, Verenaen_GB
dc.contributor.authorHauck, Christof Ren_GB
dc.date.accessioned2012-08-06T13:00:17Z-
dc.date.available2012-08-06T13:00:17Z-
dc.date.issued2011-03-18-
dc.identifier.citationPhosphatidylinositol 3'-kinase activity is critical for initiating the oxidative burst and bacterial destruction during CEACAM3-mediated phagocytosis. 2011, 286 (11):9555-66 J. Biol. Chem.en_GB
dc.identifier.issn1083-351X-
dc.identifier.pmid21216968-
dc.identifier.doi10.1074/jbc.M110.216085-
dc.identifier.urihttp://hdl.handle.net/10033/237371-
dc.description.abstractCarcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3) is an immunoglobulin-related receptor expressed on human granulocytes. CEACAM3 functions as a single chain phagocytotic receptor recognizing gram-negative bacteria such as Neisseria gonorrhoeae, which possess CEACAM-binding adhesins on their surface. The cytoplasmic domain of CEACAM3 contains an immunoreceptor tyrosine-based activation motif (ITAM)-like sequence that is phosphorylated upon receptor engagement. Here we show that the SH2 domains of the regulatory subunit of phosphatidylinositol 3'-kinase (PI3K) bind to tyrosine residue 230 of CEACAM3 in a phosphorylation-dependent manner. PI3K is rapidly recruited and directly associates with CEACAM3 upon bacterial binding as shown by FRET analysis. Although PI3K activity is not required for efficient uptake of the bacteria by CEACAM3-transfected cells or primary human granulocytes, it is critical for the stimulated production of reactive oxygen species by infected phagocytes and the intracellular degradation of CEACAM-binding bacteria. Together, our results highlight the ability of CEACAM3 to coordinate signaling events that not only mediate bacterial uptake, but also trigger the killing of internalized pathogens.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to The Journal of biological chemistryen_GB
dc.subject.meshAdhesins, Bacterialen_GB
dc.subject.meshCarcinoembryonic Antigenen_GB
dc.subject.meshGonorrheaen_GB
dc.subject.meshGranulocytesen_GB
dc.subject.meshHEK293 Cellsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshNeisseria gonorrhoeaeen_GB
dc.subject.meshPhagocytosisen_GB
dc.subject.meshPhosphatidylinositol 3-Kinasesen_GB
dc.subject.meshPhosphorylationen_GB
dc.subject.meshReactive Oxygen Speciesen_GB
dc.subject.meshRespiratory Bursten_GB
dc.subject.meshSignal Transductionen_GB
dc.subject.meshsrc Homology Domainsen_GB
dc.titlePhosphatidylinositol 3'-kinase activity is critical for initiating the oxidative burst and bacterial destruction during CEACAM3-mediated phagocytosis.en
dc.typeArticleen
dc.contributor.departmentLehrstuhl für Zellbiologie, Universität Konstanz, 78457 Konstanz, Germany.en_GB
dc.identifier.journalThe Journal of biological chemistryen_GB
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