The CD4 Receptor is Complexed in Detergent Lysates to a Protein-tyrosine Kinase (pp58) from Human T Lymphocytes

• Published in: Proceedings of the National Academy of Sciences - PNAS 1988-07, Vol.85 (14), p.5190-5194
• Main Authors: Rudd, Christopher E., Trevillyan, James M., Dasgupta, Jai Dev, Wong, Linda L., Schlossman, Stuart F.
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Amino Acid Sequence; Amino acids; Antibodies; Antibodies, Monoclonal; Antigens; Antigens, Differentiation, T-Lymphocyte - immunology; Antigens, Surface - immunology; Antiserum; Cell lines; Electrophoresis, Polyacrylamide Gel; HIV; HIV - immunology; Humans; Hydrogen-Ion Concentration; Immunosorbent Techniques; Lymphocyte Activation; Molecular Sequence Data; Molecular Weight; Myeloid cells; Peptide Fragments - immunology; Peptide Fragments - metabolism; Phosphoproteins - metabolism; Phosphorylation; Phosphoserine - metabolism; Phosphotyrosine; Protein-Tyrosine Kinases - metabolism; Receptors; Receptors, Virus - immunology; T lymphocytes; T-Lymphocytes - enzymology; T-Lymphocytes - immunology; Tyrosine - analogs & derivatives; Tyrosine - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.85.14.5190

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.