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The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.

PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine

Open access
Okazaki, Taku, Maeda, Akito, Nishimura, Hiroyuki, Kurosaki, Tomohiro, Honjo, Tasuku·2001·Proceedings of the National Academy of Sciences

Abstract

PD-1 is an immunoreceptor that belongs to the immunoglobulin (Ig) superfamily and contains two tyrosine residues in the cytoplasmic region. Studies on PD-1-deficient mice have shown that PD-1 plays critical roles in establishment and/or maintenance of peripheral tolerance, but the mode of action is totally unknown. To study the molecular mechanism for negative regulation of lymphocytes through the PD-1 receptor, we generated chimeric molecules composed of the IgG Fc receptor type IIB (FcγRIIB) extracellular region and the PD-1 cytoplasmic region and expressed them in a B lymphoma cell line, IIA1.6. Coligation of the cytoplasmic region of PD-1 with the B cell receptor (BCR) in IIA1.6 transformants inhibited BCR-mediated growth retardation, Ca 2+ mobilization, and tyrosine phosphorylation of effector molecules, including Igβ, Syk, phospholipase C-γ2 (PLCγ2), and ERK1/2, whereas phosphorylation of Lyn and Dok was not affected. Mutagenesis studies indicated that these inhibitory effects do not require the N-terminal tyrosine in the immunoreceptor tyrosine-based inhibitory motif-like sequence, but do require the other tyrosine residue in the C-terminal tail. This tyrosine was phosphorylated and recruited src homology 2-domain-containing tyrosine phosphatase 2 (SHP-2) on coligation of PD-1 with BCR. These results show that PD-1 can inhibit BCR signaling by recruiting SHP-2 to its phosphotyrosine and dephosphorylating key signal transducers of BCR signaling.

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Metadata

Authors
Okazaki, T., Maeda, A., Nishimura, H., Kurosaki, T., & Honjo, T.
Venue
Proceedings of the National Academy of Sciences
Published
2001-11-06
Volume
98
Issue
24
Pages
13866-13871
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2086397613
Cited by
848
References
31
FWCI
7.03
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine. https://app.cochat.ai/papers/10.1073/pnas.231486598
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Okazaki, T., Maeda, A., Nishimura, H., Kurosaki, T., & Honjo, T. (2001). PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.231486598

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