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Characterization of the cytoplasmic domain of CD28 in T cell activation and the regulation of HIV transcription.
Author(s) -
Henderson Andrew J,
Yang Polung,
August Avery,
Natarajan Malini
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.856.19
Subject(s) - cd28 , microbiology and biotechnology , transcription factor , transcription (linguistics) , signal transduction , phosphorylation , tyrosine phosphorylation , t cell , biology , cytoplasm , t cell receptor , jurkat cells , chemistry , immune system , biochemistry , immunology , gene , linguistics , philosophy
T cell activation requires signaling from the T cell receptor and the costimulatory receptor CD28. Protein tyrosine phosphorylation plays a crucial role in CD28 signaling. In order to understand the molecular basis for CD28 signaling and its ability to mediate HIV transcription, we have used a chimeric receptor approach. The cytoplasmic tail of CD28, with its four tyrosines (Y) at positions 173, 188, 191 and 200, is fused to the extracellular receptor of CD8, generating a CD8/28 chimeric receptor. We show that the tyrosines in the cytoplasmic tail of CD28 have different functions. Y173 inhibits T cell activation and HIV transcription, whereas, in the absence of the inhibitory signal Y188, Y191 and Y200 have increase HIV transcription. Signals recruited by Y191 and Y200 have redundant functions, are required to overcome the Y173 inhibition and are sufficient for activating HIV transcription, NF‐κB and Vav phosphorylation. Y188 activates Vav but does not induce HIV transcription. How these positive and negative signals are coordinated to influence HIV transcription will be discussed.