No T-cell tyrosine protein kinase signalling or calcium mobilization after CD4 association with HIV-1 or HIV-1 gp120

Abstract

THE T lymphocyte surface protein CD4 is an integral membrane glycoprotein noncovalently associated with the tyrosine protein kinase p56^lck (reviewed in ref. 1). In normal T cells, surface association of CD4 molecules with other CD4 molecules or other T-cell surface proteins, such as the T-cell antigen receptor, stimulates the activity of the p56^lck tyrosine kinase, resulting in the phosphory lation of various cellular proteins at tyrosine residues^2–4. Thus, the signal transduction in T cells generated through the surface engagement of CD4 is similar to that observed for the class of growth factor receptors possessing endogenous tyrosine kinase activity⁵. As CD4 is also the cellular receptor for the human immunodeficiency virus (HIV)^6,7, binding of the virus or gp120 (the virus surface protein responsible for specific CD4⁺ T-cell association) could mimic the types of immunological interactions that have previously been found to stimulate p56^lck and trigger T-cell activation pathways.We have evaluated this possibility and report here that binding of HIV-1 or the virus glycoprotein gp120 to CD4⁺ human T cells fails to elicit detectable p56^lck-dependent tyrosine kinase activation and signalling, alterations in the composition of cellular phosphotyrosine-containing proteins, or changes in intracellular Ca²⁺ concentration.