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The Granulocyte Receptor Carcinoembryonic Antigen-Related Cell Adhesion Molecule 3 (CEACAM3) Directly Associates with Vav to Promote Phagocytosis of Human Pathogens

The Granulocyte Receptor Carcinoembryonic Antigen-Related Cell Adhesion Molecule 3 (CEACAM3) Directly Associates with Vav to Promote Phagocytosis of Human Pathogens

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SCHMITTER, Tim, Stefan PILS, Vadim SAKK, Ronald FRANK, Klaus-Dieter FISCHER, Christof R. HAUCK, 2007. The Granulocyte Receptor Carcinoembryonic Antigen-Related Cell Adhesion Molecule 3 (CEACAM3) Directly Associates with Vav to Promote Phagocytosis of Human Pathogens. In: The Journal of Immunology. 178(6), pp. 3797-3805. ISSN 0022-1767. eISSN 1550-6606

@article{Schmitter2007Granu-7816, title={The Granulocyte Receptor Carcinoembryonic Antigen-Related Cell Adhesion Molecule 3 (CEACAM3) Directly Associates with Vav to Promote Phagocytosis of Human Pathogens}, year={2007}, doi={10.4049/​jimmunol.178.6.3797}, number={6}, volume={178}, issn={0022-1767}, journal={The Journal of Immunology}, pages={3797--3805}, author={Schmitter, Tim and Pils, Stefan and Sakk, Vadim and Frank, Ronald and Fischer, Klaus-Dieter and Hauck, Christof R.} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/7816"> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:37:45Z</dc:date> <dcterms:bibliographicCitation>First publ. in: The Journal of Immunology 178 (2007), 6, pp. 3797-3805</dcterms:bibliographicCitation> <dc:format>application/pdf</dc:format> <dc:contributor>Fischer, Klaus-Dieter</dc:contributor> <dcterms:rights rdf:resource="https://creativecommons.org/licenses/by-nc-nd/2.0/legalcode"/> <dc:creator>Fischer, Klaus-Dieter</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:37:45Z</dcterms:available> <dc:creator>Pils, Stefan</dc:creator> <dc:creator>Frank, Ronald</dc:creator> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/7816"/> <dc:creator>Sakk, Vadim</dc:creator> <dcterms:abstract xml:lang="eng">The human granulocyte-specific receptor carcinoembryonic antigen-related cell adhesion molecule (CEACAM)3 is critically involved in the opsonin-independent recognition of several bacterial pathogens. CEACAM3-mediated phagocytosis depends on the integrity of an ITAM-like sequence within the cytoplasmic domain of CEACAM3 and is characterized by rapid stimulation of the GTPase Rac. By performing a functional screen with CEACAM3-expressing cells, we found that overexpression of a dominant-negative form of the guanine nucleotide exchange factor Vav, but not the dominant-negative versions SWAP70, Dock2, or ELMO1 interfered with CEACAM3-initiated phagocytosis. Moreover, small interfering RNA-mediated silencing of Vav reduced uptake and abrogated the stimulation of Rac in response to bacterial CEACAM3 engagement. In Vav1/Vav2-deficient cells, CEACAM3-mediated internalization was only observed after re-expression of Vav. Vav colocalized with CEACAM3 upon bacterial infection, coimmunoprecipitated in a complex with CEACAM3, and the Vav Src homology 2 domain directly associated with phosphorylated Tyr230 of CEACAM3. In primary human granulocytes, TAT-mediated transduction of dominant-negative Vav, but not SWAP70, severely impaired the uptake of CEACAM3-binding bacteria. These data support the view that, different from canonical ITAM signaling, the CEACAM3 ITAM-like sequence short-wires bacterial recognition and Rac stimulation via a direct association with Vav to promote rapid phagocytosis and elimination of CEACAM-binding human pathogens.</dcterms:abstract> <dc:contributor>Sakk, Vadim</dc:contributor> <dc:creator>Schmitter, Tim</dc:creator> <dcterms:issued>2007</dcterms:issued> <dc:contributor>Hauck, Christof R.</dc:contributor> <dc:rights>deposit-license</dc:rights> <dc:contributor>Schmitter, Tim</dc:contributor> <dc:language>eng</dc:language> <dc:creator>Hauck, Christof R.</dc:creator> <dc:contributor>Frank, Ronald</dc:contributor> <dc:contributor>Pils, Stefan</dc:contributor> <dcterms:title>The Granulocyte Receptor Carcinoembryonic Antigen-Related Cell Adhesion Molecule 3 (CEACAM3) Directly Associates with Vav to Promote Phagocytosis of Human Pathogens</dcterms:title> </rdf:Description> </rdf:RDF>

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

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