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.