Nef enhances c-Cbl phosphorylation in HIV-infected CD4+ T lymphocytes.
The multifunctional HIV-1 protein Nef possesses several motifs that interact with signaling molecules in infected T cells. In order to determine whether Nef influences T cell activation, cells were infected with Nef-positive and Nef-negative clones of HIV. CD28 expression and changes in tyrosine phosphorylation were monitored. We observed no Nef-dependent changes in CD28 expression or function. However, infection with Nef-positive virus led to changes in tyrosine phosphorylation. This Nef-induced phosphorylation was observed in unstimulated cells, and c-Cbl was identified as one of the proteins whose phosphorylation was upregulated by Nef. Furthermore, Lck is required for Nef-mediated c-Cbl tyrosine phosphorylation. These results suggest that Nef modifies T cell signaling in the absence of T cell receptor engagement and co-stimulation.
Yang
Polung
P
Integrated Bioscience Graduate Program in Immunobiology, Department of Veterinary Science, Immunology Research Laboratories, 115 Henning Building, Pennsylvania State University, University Park, PA 16802, USA.
Henderson
Andrew J
AJ
D018106:CD28 Antigens / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D015693:Gene Products, nef / Q000172:deficiency / Q000502:physiology*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism / Q000821:virology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D014443:Tyrosine / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D015854:Up-Regulation; D054311:nef Gene Products, Human Immunodeficiency Virus
D018106:CD28 Antigens; D015693:Gene Products, nef; D011518:Proto-Oncogene Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D014443:Tyrosine; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C067419:CBL protein, human