Binding of HIV-1 to its receptor induces tyrosine phosphorylation of several CD4-associated proteins, including the phosphatidylinositol 3-kinase.
Cell surface CD4 molecules are known to be important in several physiological responses of T lymphocytes. The use of human immunodeficiency virus (HIV) particles or purified gp120 molecules as CD4 cross-linking agents has been shown to result in a cascade of intracellular biochemical events. In addition, we and other have provided evidence suggesting that virus-mediated CD4 multimerization can lead to modulation of HIV-1 long terminal repeat-dependent activity and virus production. We were thus interested in measuring the effect of HIV-1 particles on intracellular tyrosine-phosphorylation levels, mostly of CD4-associated proteins. Using the T cell line CEM-T4, we observed that HIV-1 induces an increase in tyrosine phosphorylation of four major proteins physically complexed to the CD4 molecule. Immunoblot analysis permitted the identification of two of these proteins, p56lck and phosphatidylinositol 3-kinase (PI 3-kinase) p85 alpha. No concomitant variation in the level of these two CD4-associated proteins was observed after HIV-1-induced CD4 cross-linking. To our knowledge, this is the first report linking HIV-1-mediated CD4 multimerization to an increase in tyrosine phosphorylation of the PI 3-kinase complex. The four CD4-associated molecules described in this report are most likely implicated in virus-induced CD4-linked signaling events.
Briand
G
G
Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Canada.
Barbeau
B
B
Tremblay
M
M
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
D015704:CD4 Antigens; D015728:Receptors, HIV; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases