{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:53:03Z","timestamp":1790697183949,"version":"4.1.0"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1995,1,1]]},"abstract":"<jats:p>CTLA-4 is a T cell antigen that is structurally related to CD28 and serves as a high affinity ligand for the B cell antigen B7-1\/2. Unlike CD28, the function of CTLA-4 is unclear, although reports have implicated the antigen in the costimulation of T cells. Recently, phosphatidylinositol 3-kinase (PI 3-kinase) has been implicated in the costimulatory function of CD28 by virtue of its ability to bind to a pYMNM motif within the cytoplasmic tail of the antigen. In this study, we show that CTLA-4 can also associate with PI 3-kinase as detected by lipid kinase analysis and immunoblotting with anti-p85 antiserum. High pressure liquid chromatographic separation of deacylated lipids showed the presence of a peak corresponding to PI-3-P. Anti-CTLA-4 ligation of the receptor induced a significant increase in the levels of precipitable PI 3-kinase activity. Peptide binding studies revealed that the NH2- and COOH-terminal SH2 domains of p85 bind the CTLA-4 cytoplasmic pYVKM motif with an affinity (ID50: 0.6 and 0.04 microM), that is similar to CD28. CTLA-4 binding to PI 3-kinase provides further evidence that CTLA-4 is not an inert counterreceptor, but rather is coupled to an intracellular signaling molecule with the capacity to regulate cell growth.<\/jats:p>","DOI":"10.1084\/jem.181.1.351","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"351-355","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":124,"title":["CTLA-4 binding to the lipid kinase phosphatidylinositol 3-kinase in T cells."],"prefix":"10.1084","volume":"181","author":[{"given":"H","family":"Schneider","sequence":"first","affiliation":[{"name":"Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K V","family":"Prasad","sequence":"additional","affiliation":[{"name":"Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S E","family":"Shoelson","sequence":"additional","affiliation":[{"name":"Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C E","family":"Rudd","sequence":"additional","affiliation":[{"name":"Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1995,1,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/181\/1\/351\/1676846\/351.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/181\/1\/351\/1676846\/351.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T06:39:48Z","timestamp":1690267188000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/181\/1\/351\/50516\/CTLA-4-binding-to-the-lipid-kinase"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,1,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1995,1,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.181.1.351","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,1,1]]}}}