{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:13:05Z","timestamp":1790982785200,"version":"4.1.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2003,4,1]],"date-time":"2003-04-01T00:00:00Z","timestamp":1049155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CD47 has been implicated in both positive and negative regulation of T cells as well as in T cell death. To clarify the role of CD47 in T cell function, we have studied the mechanism of T cell death in response to CD47 ligands, including mAb 1F7, thrombospondin-1, and a CD47 agonist peptide derived from it. CD47\u2212\/\u2212 Jurkat T cells (JINB8) were resistant to killing by all three ligands, indicating the essential role of CD47. Primary human T cells were also killed by CD47 ligands, but only after activation with anti-CD3. CD47-mediated cell death occurred without active caspases, DNA fragmentation, or Bcl-2 degradation. Pretreatment of Jurkat and primary T cells with pertussis toxin (PTX) prevented CD47-mediated death, indicating the involvement of Gi\u03b1. Pretreatment of T cells with 8-bromo cAMP, forskolin, or 3-isobutyl-1-methylxanthine prevented the CD47-mediated apoptosis, and 1F7 dramatically reduced intracellular cAMP levels, an effect reversed with PTX. H89 and protein kinase A (PKA) inhibitor peptide, a specific PKA inhibitor, prevented rescue of T cells by PTX, 8-bromo cAMP, and forskolin, indicating a direct role for one or more PKA substrates. Thus, CD47-mediated killing of activated T cells occurs by a novel pathway involving regulation of cAMP levels by heterotrimeric Gi\u03b1 with subsequent effects mediated by PKA.<\/jats:p>","DOI":"10.4049\/jimmunol.170.7.3544","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:28:40Z","timestamp":1398022120000},"page":"3544-3553","source":"Crossref","is-referenced-by-count":79,"title":["The Mechanism of CD47-Dependent Killing of T Cells: Heterotrimeric Gi-Dependent Inhibition of Protein Kinase A"],"prefix":"10.1093","volume":"170","author":[{"given":"Partha Pratim","family":"Manna","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A","family":"Frazier","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,4,1]]},"reference":[{"key":"2026020210071620800_R1","first-page":"4338","volume-title":"J. Immunol.","year":"1993"},{"key":"2026020210071620800_R2","first-page":"5704","volume-title":"J. Immunol.","year":"1993"},{"key":"2026020210071620800_R3","first-page":"314","volume-title":"Nature","year":"1992"},{"key":"2026020210071620800_R4","first-page":"969","volume-title":"Cell","year":"1994"},{"key":"2026020210071620800_R5","first-page":"405","volume-title":"Immunity","year":"1994"},{"key":"2026020210071620800_R6","first-page":"811","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1995"},{"key":"2026020210071620800_R7","first-page":"985","volume-title":"Science","year":"1995"},{"key":"2026020210071620800_R8","first-page":"130","volume-title":"Trends Cell Biol.","year":"2001"},{"key":"2026020210071620800_R9","first-page":"357","volume-title":"Am. Heart J.","year":"1998"},{"key":"2026020210071620800_R10","first-page":"1068","volume-title":"Am. J. Pathol.","year":"1995"},{"key":"2026020210071620800_R11","first-page":"2785","volume-title":"J. Cell Biol.","year":"1990"},{"key":"2026020210071620800_R12","first-page":"533","volume-title":"J. Cell Biol.","year":"1996"},{"key":"2026020210071620800_R13","first-page":"14740","volume-title":"J. Biol. Chem.","year":"1997"},{"key":"2026020210071620800_R14","first-page":"3978","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1995"},{"key":"2026020210071620800_R15","first-page":"437","volume-title":"J. Cell Biol.","year":"1996"},{"key":"2026020210071620800_R16","first-page":"677","volume-title":"J. Immunol.","year":"1997"},{"key":"2026020210071620800_R17","first-page":"1","volume-title":"J. Exp. Med.","year":"1997"},{"key":"2026020210071620800_R18","first-page":"4624","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020210071620800_R19","first-page":"2459","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210071620800_R20","first-page":"5345","volume-title":"J. Immunol.","year":"1997"},{"key":"2026020210071620800_R21","first-page":"2193","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020210071620800_R22","first-page":"2427","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210071620800_R23","first-page":"7031","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020210071620800_R24","first-page":"1277","volume-title":"Nat. Med.","year":"1999"},{"key":"2026020210071620800_R25","first-page":"8554","volume-title":"J. Biol. Chem.","year":"1999"},{"key":"2026020210071620800_R26","first-page":"673","volume-title":"J. Cell Biol.","year":"1999"},{"key":"2026020210071620800_R27","first-page":"3621","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020210071620800_R28","first-page":"389","volume-title":"J. Cell Biol.","year":"1999"},{"key":"2026020210071620800_R29","first-page":"642","volume-title":"Blood","year":"1999"},{"key":"2026020210071620800_R30","first-page":"485","volume-title":"J. Cell Biol.","year":"1993"},{"key":"2026020210071620800_R31","first-page":"3419","volume-title":"J. Cell Sci.","year":"1995"},{"key":"2026020210071620800_R32","first-page":"707","volume-title":"Int. Immunol.","year":"1999"},{"key":"2026020210071620800_R33","first-page":"1563","volume-title":"Transplantation","year":"2001"},{"key":"2026020210071620800_R34","first-page":"1661","volume-title":"J. Exp. Med.","year":"1995"},{"key":"2026020210071620800_R35","first-page":"1155","volume-title":"J. Exp. Med.","year":"1996"},{"key":"2026020210071620800_R36","first-page":"249","volume-title":"Cell","year":"1995"},{"key":"2026020210071620800_R37","first-page":"45041","volume-title":"J. Biol. Chem.","year":"2001"},{"key":"2026020210071620800_R38","first-page":"6736","volume-title":"J. Biol. Chem.","year":"1998"},{"key":"2026020210071620800_R39","first-page":"637","volume-title":"J. Cell Sci.","year":"1998"},{"key":"2026020210071620800_R40","first-page":"661","volume-title":"Cell Death Differ.","year":"1999"},{"key":"2026020210071620800_R41","first-page":"509","volume-title":"J. Cell Biol.","year":"2002"},{"key":"2026020210071620800_R42","first-page":"931","volume-title":"Nat. Cell Biol.","year":"2000"},{"key":"2026020210071620800_R43","first-page":"S97","volume-title":"Cell","year":"2002"},{"key":"2026020210071620800_R44","first-page":"215","volume-title":"J. Cell Biol.","year":"1997"},{"key":"2026020210071620800_R45","first-page":"1309","volume-title":"Science","year":"1998"},{"key":"2026020210071620800_R46","first-page":"1531","volume-title":"J. Exp. Med.","year":"1999"},{"key":"2026020210071620800_R47","first-page":"356","volume-title":"Pigm. Cell. Res.","year":"2001"},{"key":"2026020210071620800_R48","first-page":"139","volume-title":"Biochim. Biophys. Acta","year":"2002"},{"key":"2026020210071620800_R49","first-page":"24896","volume-title":"J. Biol. Chem.","year":"2002"},{"key":"2026020210071620800_R50","first-page":"413","volume-title":"Mol. Cell.","year":"1999"},{"key":"2026020210071620800_R51","first-page":"24141","volume-title":"J. Biol. Chem.","year":"1997"},{"key":"2026020210071620800_R52","first-page":"459","volume-title":"J. Cell Biol.","year":"2001"},{"key":"2026020210071620800_R53","first-page":"3500","volume-title":"Blood","year":"2002"},{"key":"2026020210071620800_R54","first-page":"541","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2026020210071620800_R55","first-page":"795","volume-title":"Science","year":"1996"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/170\/7\/3544\/62565080\/3544.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/170\/7\/3544\/62565080\/3544.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T15:09:06Z","timestamp":1770044946000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/170\/7\/3544\/8028250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,4,1]]},"references-count":55,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2003,4,1]]},"published-print":{"date-parts":[[2003,4,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.170.7.3544","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2003,4]]},"published":{"date-parts":[[2003,4,1]]}}}