{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:58:01Z","timestamp":1779343081800,"version":"3.51.4"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1994,6,1]]},"abstract":"<jats:p>CD40 plays an important role in B cell activation, proliferation, and Ig class switching. The signal transduction pathway mediated by CD40 was studied using monoclonal antibody (mAb) 626.1 to CD40. Burkitt's lymphoma and Epstein-Barr virus-transformed B cell lines and tonsilar B lymphocytes were treated with the anti-CD40 mAb for various lengths of time. The early events triggered by CD40 were examined by monitoring the changes in tyrosine phosphorylation of cellular proteins with anti-phosphotyrosine mAb. Dephosphorylation of specific proteins ranging between 50-110 kD and the appearance of a 28-kD tyrosine phosphorylated protein were seen within 30 s in human B cell lines. The dephosphorylation was reversed and the 28-kD protein was dephosphorylated in cells stimulated for 1 min. In resting B cells, the appearance of the 28-kD phosphoprotein was observed in 30 s after the addition of the anti-CD40 mAb. The tyrosine phosphorylation of this protein persisted. The patterns of protein tyrosine phosphorylation differed from those induced by an anti-immunoglobulin M mAb. The changes in the state of tyrosine phosphorylation induced by the anti-CD40 mAb were obviated by mAb to CD45, a protein tyrosine phosphatase (PTP) or by the addition of sodium orthovanadate, a broad PTP inhibitor. They were also blocked by protein tyrosine kinase (PTK) inhibitors, herbimycin A and genistein, and PKC and protein serine\/threonine kinase inhibitors, H7 and HA1004. In addition, the alteration in the tyrosine phosphorylation of PTKs Lyn, Fyn, and Syk was directly demonstrated. Engagement of CD40 for 30 s induced a transient decrease in tyrosine phosphorylation of these PTKs. These results indicate that the early events in CD40 signaling involve the complex interaction between PTP and protein kinases.<\/jats:p>","DOI":"10.1084\/jem.179.6.1923","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"1923-1931","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":87,"title":["CD40 signaling pathway: anti-CD40 monoclonal antibody induces rapid dephosphorylation and phosphorylation of tyrosine-phosphorylated proteins including protein tyrosine kinase Lyn, Fyn, and Syk and the appearance of a 28-kD tyrosine phosphorylated protein."],"prefix":"10.1084","volume":"179","author":[{"given":"M","family":"Faris","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Virginia Cancer Center, University of Virginia School of Medicine, Charlottesville 22908."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Gaskin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Virginia Cancer Center, University of Virginia School of Medicine, Charlottesville 22908."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J T","family":"Parsons","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Virginia Cancer Center, University of Virginia School of Medicine, Charlottesville 22908."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S M","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Virginia Cancer Center, University of Virginia School of Medicine, Charlottesville 22908."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1994,6,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/179\/6\/1923\/1675890\/1923.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/179\/6\/1923\/1675890\/1923.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T06:07:48Z","timestamp":1690265268000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/179\/6\/1923\/24978\/CD40-signaling-pathway-anti-CD40-monoclonal"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,6,1]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1994,6,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.179.6.1923","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,6,1]]}}}