{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:35:59Z","timestamp":1780104959957,"version":"3.54.0"},"reference-count":30,"publisher":"Proceedings of the National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,11,20]]},"abstract":"<jats:p>\n            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 (Fc\u03b3RIIB) 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\n            <jats:sup>2+<\/jats:sup>\n            mobilization, and tyrosine phosphorylation of effector molecules, including Ig\u03b2, Syk, phospholipase C-\u03b32 (PLC\u03b32), 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.\n          <\/jats:p>","DOI":"10.1073\/pnas.231486598","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:35:07Z","timestamp":1027694107000},"page":"13866-13871","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":714,"title":["PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine"],"prefix":"10.1073","volume":"98","author":[{"given":"Taku","family":"Okazaki","sequence":"first","affiliation":[{"name":"Department of Medical Chemistry and Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan; and Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akito","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry and Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan; and Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry and Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan; and Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Kurosaki","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry and Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan; and Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasuku","family":"Honjo","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry and Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan; and Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,11,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05481.x"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1994.1562"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60019-X"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(97)80079-9"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/8.5.765"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/8.5.773"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/10.10.1563"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80089-8"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5502.319"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.7.1027"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90115-5"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5288.798"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80124-7"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00027-3"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(95)80103-0"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80337-2"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80509-9"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202552"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-5710(98)00025-5"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701984"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80187-9"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.50.35855"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/85330"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.7.839"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/70932"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.6.1809"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(00)00089-3"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)80042-9"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.20.13066"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/386181a0"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.231486598","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:04:11Z","timestamp":1649855051000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.231486598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,11,6]]},"references-count":30,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2001,11,20]]}},"alternative-id":["10.1073\/pnas.231486598"],"URL":"https:\/\/doi.org\/10.1073\/pnas.231486598","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,11,6]]},"assertion":[{"value":"2001-09-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-11-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}