Publikation: Phagocytosis mediated by the human granulocyte receptor CEACAM3 is limited by the receptor-type protein tyrosine phosphatase PTPRJ
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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.
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GOOB, 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.2022.102269BibTex
@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} }
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