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

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2011

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Journal of Biological Chemistry. 2011, 286(11), pp. 9555-9566. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1074/jbc.M110.216085

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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.

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570 Biowissenschaften, Biologie

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ISO 690BUNTRU, Alexander, Kathrin KOPP, Maike VOGES, Roland FRANK, Verena BACHMANN, Christof R. HAUCK, 2011. Phosphatidylinositol 3'-kinase activity is critical for initiating the oxidative burst and bacterial destruction during CEACAM3-mediated phagocytosis. In: Journal of Biological Chemistry. 2011, 286(11), pp. 9555-9566. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1074/jbc.M110.216085
BibTex
@article{Buntru2011-03-18Phosp-16828,
  year={2011},
  doi={10.1074/jbc.M110.216085},
  title={Phosphatidylinositol 3'-kinase activity is critical for initiating the oxidative burst and bacterial destruction during CEACAM3-mediated phagocytosis},
  number={11},
  volume={286},
  issn={0021-9258},
  journal={Journal of Biological Chemistry},
  pages={9555--9566},
  author={Buntru, Alexander and Kopp, Kathrin and Voges, Maike and Frank, Roland and Bachmann, Verena and Hauck, Christof R.}
}
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