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dc.contributor.authorBuntru, Alexander
dc.contributor.authorKopp, Kathrin
dc.contributor.authorVoges, Maike
dc.contributor.authorFrank, Ronald
dc.contributor.authorBachmann, Verena
dc.contributor.authorHauck, Christof R
dc.date.accessioned2017-02-16T15:07:54Z
dc.date.available2017-02-16T15:07:54Z
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
dc.identifier.issn1083-351X
dc.identifier.pmid21216968
dc.identifier.doi10.1074/jbc.M110.216085
dc.identifier.urihttp://hdl.handle.net/10033/620825
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.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAdhesins, Bacterialen
dc.subject.meshCarcinoembryonic Antigenen
dc.subject.meshGonorrheaen
dc.subject.meshGranulocytesen
dc.subject.meshHEK293 Cellsen
dc.subject.meshHumansen
dc.subject.meshNeisseria gonorrhoeaeen
dc.subject.meshPhagocytosisen
dc.subject.meshPhosphatidylinositol 3-Kinasesen
dc.subject.meshPhosphorylationen
dc.subject.meshReactive Oxygen Speciesen
dc.subject.meshRespiratory Bursten
dc.subject.meshSignal Transductionen
dc.subject.meshsrc Homology Domainsen
dc.titlePhosphatidylinositol 3'-kinase activity is critical for initiating the oxidative burst and bacterial destruction during CEACAM3-mediated phagocytosis.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalThe Journal of biological chemistryen
refterms.dateFOA2018-06-13T01:30:57Z
html.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.


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