{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:56:32Z","timestamp":1768902992045,"version":"3.49.0"},"reference-count":53,"publisher":"The Royal Society","issue":"1299","license":[{"start":{"date-parts":[[1993,10,29]],"date-time":"1993-10-29T00:00:00Z","timestamp":751852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1993,10,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CD4 serves as a receptor for MHC class II antigens and as a receptor for the hum an immunodeficiency virus (HIV -1) viral coat protein gp120. It is coupled to the protein-tyrosine kinase p56lck, an interaction necessary for an optimal response of certain T cells to antigen. Although anti-CD4 crosslinking may increase lck activity, the effects of HIV-1 gp120 have been controversial. Activated protein-tyrosine kinases are known to associate with certain intracellular proteins possessing src-homology regions (SH-2 domains) such as phosphatidylinositol 3-kinase (PI 3-kinase). In this paper, we demonstrate that the CD4:p56lck complex associates with significant amounts of phosphatidylinositol (PI) kinase activity. High pressure liquid chromatographic (HPLC) analysis of the reaction products dem onstrated the presence of phosphatidylinositol 3-phosphate (PI 3-P) and phosphatidylinositol 4-phosphate (PI 4-P), thus indicating that PI 3 and PI 4 kinases associate with CD4-p56lck. T he p85 subunit of PI 3-kinase was also detected in anti-CD4 immunoprecipitates by immunoblotting with anti-p85 antiserum . Significantly, p56lck binding to CD4 appears to be necessary for the detection of lipid kinase activity associated with p56lck. Also, anti-HIV gpl20 and anti-CD4 crosslinking induced a 10-15-fold increase in levels of both PI 3- and PI 4-kinase activity in anti-CD4 precipitates. Stimulation of CD4-p56lck-linked PI kinases by crosslinked HIV-1 gpl20 may play a role in H IV -l-induced immune defects.<\/jats:p>","DOI":"10.1098\/rstb.1993.0132","type":"journal-article","created":{"date-parts":[[2006,12,18]],"date-time":"2006-12-18T19:03:09Z","timestamp":1166468589000},"page":"35-42","source":"Crossref","is-referenced-by-count":6,"title":["Regulation of CD4-p561ck-associated phosphatidylinositol 3-kinase (PI 3-kinase) and phosphatidylinositol 4-kinase (PI 4-kinase)"],"prefix":"10.1098","volume":"342","author":[{"given":"K.v.s.","family":"Prasad","sequence":"first","affiliation":[{"name":"Divisions of Tumor Immunology, Dana-Farber Cancer Institute, Boston 02115, U. S. A."},{"name":"Department of Pathology, Harvard Medical School, Boston, and Department of Physiology, Tufts University Medical School, Boston 02111, U. S. A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosana","family":"Kapeller","sequence":"additional","affiliation":[{"name":"Division of Signal Transduction, Beth Israel Hospital, Boston 02115, U. S. A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ottmar","family":"Janssen","sequence":"additional","affiliation":[{"name":"Divisions of Tumor Immunology, Dana-Farber Cancer Institute, Boston 02115, U. S. A."},{"name":"Department of Pathology, Harvard Medical School, Boston, and Department of Physiology, Tufts University Medical School, Boston 02111, U. S. A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan S.","family":"Duke-Cohan","sequence":"additional","affiliation":[{"name":"Divisions of Tumor Immunology, Dana-Farber Cancer Institute, Boston 02115, U. S. A."},{"name":"Department of Pathology, Harvard Medical School, Boston, and Department of Physiology, Tufts University Medical School, Boston 02111, U. S. A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heinrich","family":"Repke","sequence":"additional","affiliation":[{"name":"Tumor Immunology, Dana-Farber Cancer Institute, Boston 02115, U. S. A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lewis C.","family":"Cantley","sequence":"additional","affiliation":[{"name":"Division of Signal Transduction, Beth Israel Hospital, Boston 02115, U. S. A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher E.","family":"Rudd","sequence":"additional","affiliation":[{"name":"Divisions of Tumor Immunology, Dana-Farber Cancer Institute, Boston 02115, U. S. A."},{"name":"Department of Pathology, Harvard Medical School, Boston, and Department of Physiology, Tufts University Medical School, Boston 02111, U. S. A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","reference":[{"key":"p_1","first-page":"63","article-title":"E n h an c em ent of T-cell responsiveness by the Iym phocyte-specific tyrosine protein kinase p561ck. Nature","volume":"350","author":"Miceli M .","year":"1991","journal-title":"Lond."},{"key":"p_2","first-page":"678","article-title":"Crosslinking o f T 3 (CD3) an d T 4 (CD4) enhances the proliferation of resting T Iym phocytes. J","volume":"139","year":"1987","journal-title":"Immunol."},{"key":"p_3","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90182-7"},{"key":"p_4","first-page":"4431","article-title":"Interleukin 2- and polyom a virus m iddle T antigeninduced m odification o f phosphatidyl inositol 3-kinase activity in activated T Iym phocytes. 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