Publikation:

Phagocytosis mediated by the human granulocyte receptor CEACAM3 is limited by the receptor-type protein tyrosine phosphatase PTPRJ

Lade...
Vorschaubild

Dateien

Goob_2-18lo7h9wwruw40.pdf
Goob_2-18lo7h9wwruw40.pdfGröße: 2.08 MBDownloads: 111

Datum

2022

Herausgeber:innen

Kontakt

ISSN der Zeitschrift

Electronic ISSN

ISBN

Bibliografische Daten

Verlag

Schriftenreihe

Auflagebezeichnung

ArXiv-ID

Internationale Patentnummer

Link zur Lizenz

Angaben zur Forschungsförderung

Projekt

Open Access-Veröffentlichung
Open Access Gold
Core Facility der Universität Konstanz

Gesperrt bis

Titel in einer weiteren Sprache

Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published

Erschienen in

Journal of Biological Chemistry. Elsevier. 2022, 298(9), 102269. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1016/j.jbc.2022.102269

Zusammenfassung

Carcinoembryonic Antigen-related Cell Adhesion Molecule 3 (CEACAM3) is a human granulocyte receptor mediating the efficient phagocytosis of a subset of human-restricted bacterial pathogens. Its function depends on phosphorylation of a tyrosine-based sequence motif, but the enzyme(s) responsible for reversing this modification are unclear. Here, we identify the receptor-type protein tyrosine phosphatase PTPRJ as a negative regulator of CEACAM3-mediated phagocytosis. We show depletion of PTPRJ results in a gain-of-function phenotype, while overexpression of a constitutively active PTPRJ phosphatase strongly reduces bacterial uptake via CEACAM3. We also determined that recombinant PTPRJ directly dephosphorylates the cytoplasmic tyrosine residues of purified full-length CEACAM3 and recognizes synthetic CEACAM3-derived phospho-peptides as substrates. Dephosphorylation of CEACAM3 by PTPRJ is also observed in intact cells, thereby limiting receptor-initiated cytoskeletal re-arrangements, lamellipodia formation, and bacterial uptake. Finally, we show that human phagocytes deficient for PTPRJ exhibit exaggerated lamellipodia formation and enhanced opsonin-independent phagocytosis of CEACAM3-binding bacteria. Taken together, our results highlight PTPRJ as a bona fide negative regulator of CEACAM3-initiated phagocyte functions, revealing a potential molecular target to limit CEACAM3-driven inflammatory responses.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

CEACAM, protein phosphatase, tyrosine phosphorylation, protein kinase, phagocytosis, pathogenic bacteria

Konferenz

Rezension
undefined / . - undefined, undefined

Forschungsvorhaben

Organisationseinheiten

Zeitschriftenheft

Zugehörige Datensätze in KOPS

Zitieren

ISO 690GOOB, Griseldis, Jonas ADRIAN, Chiara COSSU, Christof R. HAUCK, 2022. Phagocytosis mediated by the human granulocyte receptor CEACAM3 is limited by the receptor-type protein tyrosine phosphatase PTPRJ. In: Journal of Biological Chemistry. Elsevier. 2022, 298(9), 102269. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1016/j.jbc.2022.102269
BibTex
@article{Goob2022-09Phago-58069,
  year={2022},
  doi={10.1016/j.jbc.2022.102269},
  title={Phagocytosis mediated by the human granulocyte receptor CEACAM3 is limited by the receptor-type protein tyrosine phosphatase PTPRJ},
  number={9},
  volume={298},
  issn={0021-9258},
  journal={Journal of Biological Chemistry},
  author={Goob, Griseldis and Adrian, Jonas and Cossu, Chiara and Hauck, Christof R.},
  note={This study was supported by funds from the Deutsche Forschungsgemeinschaft (Ha 2856/10–1) to C. R. H. Article Number: 102269}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/58069">
    <dc:contributor>Hauck, Christof R.</dc:contributor>
    <dc:contributor>Cossu, Chiara</dc:contributor>
    <dcterms:title>Phagocytosis mediated by the human granulocyte receptor CEACAM3 is limited by the receptor-type protein tyrosine phosphatase PTPRJ</dcterms:title>
    <dc:creator>Cossu, Chiara</dc:creator>
    <dc:creator>Hauck, Christof R.</dc:creator>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/58069"/>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/58069/1/Goob_2-18lo7h9wwruw40.pdf"/>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:creator>Goob, Griseldis</dc:creator>
    <dc:language>eng</dc:language>
    <dc:creator>Adrian, Jonas</dc:creator>
    <dc:contributor>Goob, Griseldis</dc:contributor>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/58069/1/Goob_2-18lo7h9wwruw40.pdf"/>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-07-19T07:40:35Z</dc:date>
    <dcterms:issued>2022-09</dcterms:issued>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dcterms:abstract xml:lang="eng">Carcinoembryonic Antigen-related Cell Adhesion Molecule 3 (CEACAM3) is a human granulocyte receptor mediating the efficient phagocytosis of a subset of human-restricted bacterial pathogens. Its function depends on phosphorylation of a tyrosine-based sequence motif, but the enzyme(s) responsible for reversing this modification are unclear. Here, we identify the receptor-type protein tyrosine phosphatase PTPRJ as a negative regulator of CEACAM3-mediated phagocytosis. We show depletion of PTPRJ results in a gain-of-function phenotype, while overexpression of a constitutively active PTPRJ phosphatase strongly reduces bacterial uptake via CEACAM3. We also determined that recombinant PTPRJ directly dephosphorylates the cytoplasmic tyrosine residues of purified full-length CEACAM3 and recognizes synthetic CEACAM3-derived phospho-peptides as substrates. Dephosphorylation of CEACAM3 by PTPRJ is also observed in intact cells, thereby limiting receptor-initiated cytoskeletal re-arrangements, lamellipodia formation, and bacterial uptake. Finally, we show that human phagocytes deficient for PTPRJ exhibit exaggerated lamellipodia formation and enhanced opsonin-independent phagocytosis of CEACAM3-binding bacteria. Taken together, our results highlight PTPRJ as a bona fide negative regulator of CEACAM3-initiated phagocyte functions, revealing a potential molecular target to limit CEACAM3-driven inflammatory responses.</dcterms:abstract>
    <dc:contributor>Adrian, Jonas</dc:contributor>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-07-19T07:40:35Z</dcterms:available>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by-nc-nd/4.0/"/>
    <dc:rights>Attribution-NonCommercial-NoDerivatives 4.0 International</dc:rights>
  </rdf:Description>
</rdf:RDF>

Interner Vermerk

xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter

Kontakt
URL der Originalveröffentl.

Prüfdatum der URL

Prüfungsdatum der Dissertation

Finanzierungsart

Kommentar zur Publikation

This study was supported by funds from the Deutsche Forschungsgemeinschaft (Ha 2856/10–1) to C. R. H.
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Ja
Diese Publikation teilen