Recruitment of Phosphatidylinositol 3-Kinase to CD28 Inhibits HIV Transcription by a Tat-Dependent Mechanism

Cook, Julie A.; August, Avery; Henderson, Andrew J.

doi:10.4049/jimmunol.169.1.254

Cited by 16 publications

(38 citation statements)

References 68 publications

(64 reference statements)

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“…Several CD28 tyrosine phosphorylation sites have been described in the literature. Tyr 191 in the YMNM motif of the CD28 cytoplasmic tail (7,8) has been shown to recruit PI3K and negatively regulate HIV-1 transcription (29). Tyr 218 in CD28 was also shown to be involved in Vav-1 tyrosine phosphorylation, Rac1 activity (30) and, along with Tyr 206 and Tyr 209 , in IL-2 secretion (31).…”

Section: Regulation Of Tyrosine Phosphorylation In Components Of Cd28mentioning

confidence: 99%

Quantitative Analysis of Phosphotyrosine Signaling Networks Triggered by CD3 and CD28 Costimulation in Jurkat Cells

Kim

White

2006

The Journal of Immunology

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The mechanism by which stimulation of coreceptors such as CD28 contributes to full activation of TCR signaling pathways has been intensively studied, yet quantitative measurement of costimulation effects on functional TCR signaling networks has been lacking. In this study, phosphotyrosine networks triggered by CD3, CD28, or CD3 and CD28 costimulation were analyzed by site-specific quantitative phosphoproteomics, resulting in identification of 101 tyrosine and 3 threonine phosphorylation sites and quantification of 87 sites across four cell states. As expected, CD3 stimulation induced phosphorylation of CD3 chains and upstream components of TCR pathways such as Zap70, while CD28 stimulation induced phosphorylation of CD28, Vav-1, and other adaptor proteins including downstream of tyrosine kinase 1, Grb2-associated protein 2 (Grap2), and Wiskott-Aldrich syndrome protein. CD3 and CD28 costimulation induced a complex response including decreased threonine phosphorylation in the ERK1 and ERK2 activation loops and increased phosphorylation of selected tyrosine sites on ERK1/2, p38, phospholipase C-γ, Src homology 2 domain-containing transforming protein 1, Grap2, and Vav-1, potentiating T cell activation. Hierarchical clustering and self-organizing maps were used to identify modules of coregulated phosphorylation sites within the network. Quantitative information in our study suggests quantitative and qualitative contribution by costimulation of CD28 on CD3-stimulated TCR signaling networks via enhanced phosphorylation of phospholipase C-γ/Src homology 2 domain-containing transforming protein 1/Grap2/Vav-1 and their effects on downstream components including MAPKs.

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Section: Regulation Of Tyrosine Phosphorylation In Components Of Cd28mentioning

confidence: 99%

Quantitative Analysis of Phosphotyrosine Signaling Networks Triggered by CD3 and CD28 Costimulation in Jurkat Cells

Kim

White

2006

The Journal of Immunology

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“…The G-protein-coupled receptor, GPR30, is a recently identified receptor shown to bind E2 with high affinity leading to the activation of MAP kinase 57 and PI3 kinase pathways in MCF-7 cells. 58 PI3K activation has been shown to inhibit Tat-induced LTR activation 59 and GPR30 is expressed and is activated by E2 in SVGA cells (unpublished observations). Therefore a role for GPR30 in mediating the effects of estrogen in the attenuation of HIV transcription cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Receptor Alpha Inhibits the Estrogen-Mediated Suppression of HIV Transcription in Astrocytes: Implications for Estrogen Neuroprotection in HIV Dementia

Heron

Turchan–Cholewo

Bruce‐Keller

et al. 2009

AIDS Research and Human Retroviruses

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“…It is thought to bind to cellular factors and mediate their phosphorylation. This results in an increase in transcription of all HIV genes [34]. Tat has been shown to induce OS [35].…”

Section: Tatmentioning

confidence: 99%

Oxidants and Antioxidants in the Pathogenesis of HIV/AIDS

Agarwal¹

2011

TORSJ

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Human immunodeficiency virus (HIV) has predominantly been considered the main cause in the progression of acquired immunodeficiency syndrome (AIDS). However, many researchers believe that there are co-factors involved along the way that may play a critical role in its development. Elevated levels of reactive oxygen species (ROS) have been established to be present at the onset of infection. Additionally, the delayed response by the immune system upon infection may be due to an initial depletion of antioxidants, which play a critical role in scavenging excess ROS to maintain normal physiological conditions. This pro-oxidant/antioxidant imbalance results in a condition known as oxidative stress (OS). OS has been reported to be an integral element in the progression of many diseases, including AIDS. Therefore, it is presumed that antioxidant treatment may provide a promising and cost-effective therapeutic approach in treating HIV-infected individuals on a global scale.Although HIV infection presents one of the most arduous complications to humans worldwide, awareness of its origin, adverse effects, and potential treatment remain confined to a limited population. The aim of this article is to inform the reader of how AIDS developed into a global epidemic so rapidly, while emphasizing the relationship between oxidants and antioxidants in the pathogenesis of HIV/AIDS. A basic review of reduction/oxidation (redox) reactions is provided to understand how such simple introductory concepts can have such profound effects on the body. This serves as an essential building block to the topics that follow: ROS, antioxidants, and OS in HIV disease. Moreover, it allows for us to better define and elucidate OS as an often-overlooked link between HIV-infection and the progression of AIDS, as well as potential antioxidant treatment.

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Recruitment of Phosphatidylinositol 3-Kinase to CD28 Inhibits HIV Transcription by a Tat-Dependent Mechanism

Cited by 16 publications

References 68 publications

Quantitative Analysis of Phosphotyrosine Signaling Networks Triggered by CD3 and CD28 Costimulation in Jurkat Cells

Quantitative Analysis of Phosphotyrosine Signaling Networks Triggered by CD3 and CD28 Costimulation in Jurkat Cells

Estrogen Receptor Alpha Inhibits the Estrogen-Mediated Suppression of HIV Transcription in Astrocytes: Implications for Estrogen Neuroprotection in HIV Dementia

Oxidants and Antioxidants in the Pathogenesis of HIV/AIDS

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