Activation of the T-cell receptor signaling pathway by Nef from an aggressive strain of simian immunodeficiency virus. NLM AIDSLINE Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

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Activation of the T-cell receptor signaling pathway by Nef from an aggressive strain of simian immunodeficiency virus.

J Virol. 1997 Dec;71(12):9531-7. Unique Identifier : AIDSLINE MED/98037667
Luo W; Peterlin BM; Department of Medicine, Microbiology and Immunology, Howard Hughes; Medical Institute, University of California at San Francisco,; 94143-0703, USA.

Abstract: The Nef from a highly virulent strain of simian immunodeficiency virus (SIV), SIVpbj14, and a Nef from the traditional strain SIVmac239 bearing the mutation from RQ to YE (YE-Nef) both induce an acute lethal disease in monkeys. The YE mutation and its surrounding sequence resemble the immunoreceptor tyrosine-based activation motif (ITAM), which is present in the cytoplasmic tail of T- and B-cell antigen receptors and mediates signaling during lymphocyte activation. We show here that the ITAM from YE-Nef performs the same function. First, not only does YE-Nef increase the activity of the transcription factor NFAT, which is one of the downstream targets of T-cell activation, but the ITAM from the YE-Nef by itself also activates NFAT. Second, the ITAM from YE-Nef is phosphorylated on tyrosine residues by Lck and associates with ZAP-70, a T-cell-specific tyrosine kinase. The phosphorylation of both conserved tyrosine residues on the ITAM is required for the recruitment of ZAP-70. Finally, Lck is required for the activation of NFAT by YE-Nef. These results demonstrate that YE-Nef contains a functional ITAM and elucidate the molecular mechanisms underlying the pathogenesis of SIVpbj14.
Keywords: *Gene Products, nef/METABOLISM *Lymphocyte Transformation *Receptors, Antigen, T-Cell/METABOLISM *Signal Transduction *SIV/METABOLISMKWDgeneproducts,nef/metabolismKWDlymphocytetransformationKWDreceptors,antigen,t-cell/metabolismKWDsignaltransductionKWDsiv/metabolism
980330
M9831176

Copyright © 1998 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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