Two Distinct Intracytoplasmic Regions of the T-cell Adhesion Molecule CD28 Participate in Phosphatidylinositol 3-Kinase Association

Pagès, Françoise; Ragueneau, Marguerite; Klasen, Sandrine; Battifora, M.; Couez, Dominique; Sweet, Ray; Truneh, Alemseged; Ward, Stephen G.; Olive, Daniel

doi:10.1074/jbc.271.16.9403

Cited by 60 publications

(63 citation statements)

References 46 publications

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“…Therefore, CTLA-4 and CD28 appear to share a common target in intracellular signaling. This is consistent with our previous observation that both receptors bind to PI3-K (14,36,37). In fact, PI3-kinase is required for JNK activation (38).…”

Section: Resultssupporting

confidence: 93%

Cutting Edge: CTLA-4 (CD152) Differentially Regulates Mitogen-Activated Protein Kinases (Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase) in CD4+ T Cells from Receptor/Ligand-Deficient Mice

Schneider

Mandelbrot

Greenwald

et al. 2002

The Journal of Immunology

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Although CTLA-4 (CD152) has potent inhibitory effects on T cell function, the signaling events affected by this coreceptor remain to be fully defined. Mitogen-activated protein kinases (MAPK) extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) act as crucial regulators of multiple aspects of cell function. Ab ligation studies have reported an inhibitory effect of CTLA-4 on TCR-induced ERK and JNK activation. In this study, we have re-examined the specificity of CTLA-4 inhibition of MAPKs by using natural ligand with ex vivo-purified CD4+ T cells deficient in CD80 and CD86 (double knockout), or CTLA-4, CD80, and CD86 (triple knockout). Under these conditions, CTLA-4 ligation was found to up-regulate and sustain JNK activation, while inhibiting ERK activity. At the same time, JNK activation could not account for CTLA-4 induction of TGF-β production. Our findings demonstrate that CTLA-4 cosignaling is more complex than previously appreciated, with an ability to differentially regulate members of the MAPK family in T cells.

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Section: Resultssupporting

confidence: 93%

Cutting Edge: CTLA-4 (CD152) Differentially Regulates Mitogen-Activated Protein Kinases (Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase) in CD4+ T Cells from Receptor/Ligand-Deficient Mice

Schneider

Mandelbrot

Greenwald

et al. 2002

The Journal of Immunology

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“…The YMNM and the C-terminal YQPYAPP motif have been involved in the activation of both NF-jB [18,20] and, as previously demonstrated by Pages et al [21], in PI3K binding to CD28. Consistently, pre-treatment of J1G5 cells with a specific PI3K inhibitor (LY294002), before activation with Dap3/B7 cells, completely inhibited the recruitment of RelA on the HIV-1 LTR, similarly to the proteasome and NF-jB inhibitor MG132 (Fig.…”

Section: Resultssupporting

confidence: 57%

CD28 ligation in the absence of TCR promotes RelA/NF‐κB recruitment and trans‐activation of the HIV‐1 LTR

et al. 2008

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CD28 is one of the most important co-stimulatory receptors necessary for full T lymphocyte activation. CD28 can act as a TCR-independent signalling unit by delivering specific signals which may induce HIV transcription and replication. However, the mechanisms by which CD28 regulates HIV expression remain largely unknown. Here we show that the TCRindependent CD28 signals lead to the trans-activation of HIV-1 LTR in an NF-jB-dependent manner. In particular, we found that CD28 engagement by B7 induces the specific recruitment of RelA/NF-jB subunit to the HIV-1 LTR promoter both in vitro and in ex vivo infected cells. The results obtained by mutating specific tyrosine residues within the CD28 cytoplasmic tail as well as by using LY294002 inhibitory drug evidenced that the recruitment and activation of the phosphatidylinositol 3-kinase/Akt signalling pathway is crucial in mediating CD28-induced HIV transcription through RelA/NF-jB.

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“…Human CD28 insert (SalI-BamHI) was excised from pH␤Apr-1-neo-CD28WT (43), and replaced with a truncated human CD28 sequence lacking the cytoplasmic tail (plasmid pHsCD28⌬30). The cytoplasmic tails of rbtCD28 or rbtCTLA4 were then inserted in-frame with the extracellular portion of human CD28 to generate chimeric proteins, where the human cytoplasmic tail was replaced by rainbow trout CD28 or CTLA4 cytoplasmic tails (plasmids phuCD28-rbtCD28 and phuCD28-rbtCTLA4, respectively).…”

Section: Plasmids and Cell Linesmentioning

confidence: 99%

Costimulatory Receptors in a Teleost Fish: Typical CD28, Elusive CTLA4

Bernard

Riteau

Hansen

et al. 2006

The Journal of Immunology

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T cell activation requires both specific recognition of the peptide-MHC complex by the TCR and additional signals delivered by costimulatory receptors. We have identified rainbow trout sequences similar to CD28 (rbtCD28) and CTLA4 (rbtCTLA4). rbtCD28 and rbtCTLA4 are composed of an extracellular Ig-superfamily V domain, a transmembrane region, and a cytoplasmic tail. The presence of a conserved ligand binding site within the V domain of both molecules suggests that these receptors likely recognize the fish homologues of the B7 family. The mRNA expression pattern of rbtCD28 and rbtCTLA4 in naive trout is reminiscent to that reported in humans and mice, because rbtCTLA4 expression within trout leukocytes was quickly up-regulated following PHA stimulation and virus infection. The cytoplasmic tail of rbtCD28 possesses a typical motif that is conserved in mammalian costimulatory receptors for signaling purposes. A chimeric receptor made of the extracellular domain of human CD28 fused to the cytoplasmic tail of rbtCD28 promoted TCR-induced IL-2 production in a human T cell line, indicating that rbtCD28 is indeed a positive costimulator. The cytoplasmic tail of rbtCTLA4 lacked obvious signaling motifs and accordingly failed to signal when fused to the huCD28 extracellular domain. Interestingly, rbtCTLA4 and rbtCD28 are not positioned on the same chromosome and thus do not belong to a unique costimulatory cluster as in mammals. Finally, our results raise questions about the origin and evolution of positive and negative costimulation in vertebrate immune systems.

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Two Distinct Intracytoplasmic Regions of the T-cell Adhesion Molecule CD28 Participate in Phosphatidylinositol 3-Kinase Association

Cited by 60 publications

References 46 publications

Cutting Edge: CTLA-4 (CD152) Differentially Regulates Mitogen-Activated Protein Kinases (Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase) in CD4+ T Cells from Receptor/Ligand-Deficient Mice

Cutting Edge: CTLA-4 (CD152) Differentially Regulates Mitogen-Activated Protein Kinases (Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase) in CD4+ T Cells from Receptor/Ligand-Deficient Mice

CD28 ligation in the absence of TCR promotes RelA/NF‐κB recruitment and trans‐activation of the HIV‐1 LTR

Costimulatory Receptors in a Teleost Fish: Typical CD28, Elusive CTLA4

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