Binding of CD4 ligands induces tyrosine phosphorylation of phosphatidylinositol-3 kinase p110 subunit.
We have previously reported that different putative CD4 ligands (anti-CD4 antibody, gp160 from HIV, synthetic peptides analogous to the residues 35-46 of HLA class II beta1 chain and residues 134-148 of HLA class II beta2 chain) down-regulate LFA-1-dependent adhesion between CD4+ T cells and HLA class II+ B cells, and also activate p56lck and the phosphatidylinositol-3 kinase (PI3-kinase) associated with the CD4-p56lck complex. It was demonstrated that the latter activation was dependent on the CD4-p56lck association. Since these results suggest a relationship between p56lck and PI3-kinase, we investigated whether PI3-kinase was tyrosine phosphorylated after CD4 binding and whether this phosphorylation was also dependent on the CD4-p56lck association. We show herein that CD4 binding increased tyrosine phosphorylation of the catalytic subunit p110 of PI3-kinase but not of the p85 subunit. Association between p56lck and PI3-kinase was constitutive, and was not modified after CD4 binding. In contrast, p110 tyrosine phosphorylation was inducible, transient and dependent on the CD4-p56lck association. The role of the tyrosine phosphorylation of p110-PI3-kinase following ligand binding to CD4 is unknown. We speculate that this event could link the activation of p56lck and of PI3-kinase after CD4 binding.
Mazerolles
F
F
INSERM U429, Hôpital Necker-Enfants Malades, Paris, France.
Fischer
A
A
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D020134:Catalytic Domain; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D015536:Down-Regulation; D006684:HLA-DR Antigens / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology; D014443:Tyrosine / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D006684:HLA-DR Antigens; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D010446:Peptide Fragments; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)