Human immunodeficiency virus type 1 glycoprotein precursor retains a CD4-p56lck complex in the endoplasmic reticulum.
The cell surface glycoprotein, CD4, is the receptor for human immunodeficiency virus (HIV) in T lymphocytes. Following HIV infection, there is reduced expression of CD4 on the cell surface, and this downregulation probably results, at least in part, from the formation of complexes containing the HIV type 1 (HIV-1) glycoprotein precursor (gp160) and CD4 that are not transported from the endoplasmic reticulum (ER). At the plasma membrane of T cells, CD4 is tightly associated with a cytoplasmic tyrosine kinase (p56lck) that is involved in T-cell activation. Using a transient expression system with HeLa cells, we show by pulse-labeling and immunoprecipitation that newly synthesized CD4 can associate with p56lck before CD4 is transported from the ER. In the presence of HIV-1 gp160, a ternary complex of gp160-CD4 and p56lck forms in the ER. Using confocal immunofluorescence microscopy, we observed complete retention of p56lck in the ER. Such mislocation of a tyrosine kinase to the cytoplasmic face of the ER could play a role in lymphocyte killing caused by HIV infection or expression of gp160 alone.
Crise
B
B
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510.
Rose
J K
JK
D001692:Biological Transport; D015704:CD4 Antigens / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000382:microbiology*; D005455:Fluorescent Antibody Technique; D015686:Gene Products, env / Q000378:metabolism*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011498:Protein Precursors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014162:Transfection
D015704:CD4 Antigens; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)