HIV infection--induced posttranslational modification of T cell signaling molecules associated with disease progression.
In attempt to elucidate the mechanism of the HIV infection induced T cell unresponsiveness, we studied signal-transducing molecules proximal to the T cell receptor (TCR) in T lymphocytes of HIV-infected individuals. Total amounts of protein tyrosine kinases (PTKs) Lck, Fyn, and ZAP-70 and the zeta chain of the TCR were found significantly decreased in T cells of symptomatic/AIDS patients as well as in T cells of individuals in acute and early asymptomatic stages of HIV infection. Unexpectedly, the detection of Lck, Fyn, and ZAP-70 was reversed after the treatment of cell lysates with dithiothreitol. This suggests that PTKs Lck, Fyn, and ZAP-70 were modified by a mechanism altering the status of sulfhydryl groups. Moreover, this mechanism seems to affect selectively T cells of HIV infected patients since B cell PTKs Syk and Lyn were detected structurally and functionally intact. Interestingly, similar alterations of signaling molecules were not detected in T cells of HIV-infected long-term asymptomatic individuals. Modification of T cell PTKs may thus underlie the HIV-induced impairment of lymphocyte function and may potentially predict disease progression.
Duke Scholars
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- src-Family Kinases
- ZAP-70 Protein-Tyrosine Kinase
- T-Lymphocytes
- Sulfhydryl Compounds
- Signal Transduction
- Receptors, Antigen, T-Cell, gamma-delta
- Receptors, Antigen, T-Cell
- Proto-Oncogene Proteins c-fyn
- Proto-Oncogene Proteins
- Protein-Tyrosine Kinases
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- src-Family Kinases
- ZAP-70 Protein-Tyrosine Kinase
- T-Lymphocytes
- Sulfhydryl Compounds
- Signal Transduction
- Receptors, Antigen, T-Cell, gamma-delta
- Receptors, Antigen, T-Cell
- Proto-Oncogene Proteins c-fyn
- Proto-Oncogene Proteins
- Protein-Tyrosine Kinases