The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes.

TLDR

CD4 is a glycoprotein on helper T cells involved in T‑cell activation, antigen recognition, and serves as an HIV receptor, raising the question of an intracellular mediator regulating CD4+ activation. The study aims to demonstrate that CD4 associates with a 55‑60 kDa protein‑tyrosine kinase in T cells. The PTK was identified using an antiserum against a synthetic peptide derived from its DNA sequence. Two‑dimensional pH‑gradient electrophoresis revealed a heterogeneous PTK population (pH 4.0‑5.0), and in‑vitro phosphorylation detected autophosphorylation at 55‑60 kDa and additional phosphorylated polypeptides at 40 and 80 kDa, underscoring the PTK’s potential role in CD4‑mediated T‑cell activation and HIV infectivity.

Abstract

The CD4 (T4) antigen is a cell-surface glycoprotein that is expressed predominantly on the surface of helper T cells and has been implicated in the regulation of T-cell activation and in the associative recognition of class II antigens of the major histocompatibility complex. In addition, the CD4 antigen appears to serve as a receptor for the human immunodeficiency virus (HIV). An important question has been whether the CD4 receptor is linked to an intracellular mediator that could regulate the activation of the CD4+ subset. In this paper, we provide preliminary evidence that the CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (PTK) of 55-60 kDa, which is expressed specifically in T cells. The PTK is the human analogue of the murine pp56LSTRA (pp56lck) and has significant homology with c-src, c-yes, and other members of the src family. The identification of the PTK associated with CD4 receptor was made by use of an antiserum to a synthetic peptide that was deduced from the DNA sequence of PTK. Two-dimensional nonequilibrium pH gradient gel electrophoresis/NaDodSO4/PAGE revealed the kinase to focus as a heterogeneous collection of spots in the pH range of 4.0-5.0. Furthermore, in vitro phosphorylation revealed the phosphorylation of two additional polypeptides at 40 and 80 kDa, in addition to the autophosphorylation of the PTK at 55-60 kDa. The potential importance of the association between the CD4 receptor and the PTK of T cells is discussed in relation to T-cell activation and HIV infectivity.