Virology. 2005 Jun 5;336(2):219-28.

Nef enhances c-Cbl phosphorylation in HIV-infected CD4+ T lymphocytes.

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Integrated Bioscience Graduate Program in Immunobiology, Department of Veterinary Science, Immunology Research Laboratories, 115 Henning Building, Pennsylvania State University, University Park, PA 16802, USA.

Abstract

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.

PMID:: 15892963; [PubMed - indexed for MEDLINE]

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The human immunodeficiency virus type 1 Nef protein binds the Src-related tyrosine kinase Lck SH2 domain through a novel phosphotyrosine independent mechanism. [Virology. 1998]
The human immunodeficiency virus type 1 Nef protein binds the Src-related tyrosine kinase Lck SH2 domain through a novel phosphotyrosine independent mechanism.
Dutartre H, Harris M, Olive D, Collette Y. Virology. 1998 Aug 1; 247(2):200-11.
Human immunodeficiency virus type 1 Nef protein inhibits activation pathways in peripheral blood mononuclear cells and T-cell lines. [J Virol. 1995]
Human immunodeficiency virus type 1 Nef protein inhibits activation pathways in peripheral blood mononuclear cells and T-cell lines.
Greenway A, Azad A, McPhee D. J Virol. 1995 Mar; 69(3):1842-50.
Negative regulation of Lck by Cbl ubiquitin ligase. [Proc Natl Acad Sci U S A. 2002]
Negative regulation of Lck by Cbl ubiquitin ligase.
Rao N, Miyake S, Reddi AL, Douillard P, Ghosh AK, Dodge IL, Zhou P, Fernandes ND, Band H. Proc Natl Acad Sci U S A. 2002 Mar 19; 99(6):3794-9.
Review Immunodeficiency viruses. Not enough sans Nef. [Curr Biol. 1994]
Review Immunodeficiency viruses. Not enough sans Nef.
Littman DR. Curr Biol. 1994 Jul 1; 4(7):618-20.
Review The role of HIV1 Nef in T-cell activation: Nef impairs induction of Th1 cytokines and interacts with the Src family tyrosine kinase Lck. [Res Virol. 1997]
Review The role of HIV1 Nef in T-cell activation: Nef impairs induction of Th1 cytokines and interacts with the Src family tyrosine kinase Lck.
Collette Y, Dutartre H, Benziane A, Olive D. Res Virol. 1997 Jan-Feb; 148(1):52-8.

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Cited by 3 PubMed Central articles

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Huang T, Xu Z, Chen L, Cai YD, Kong X. PLoS One. 2011 Mar 4; 6(3):e17291. Epub 2011 Mar 4.
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