Signal transduction by MAP kinases in T lymphocytes

Rincón, Mercedes; Flavell, Richard A.; Davis, Roger J.

doi:10.1038/sj.onc.1204382

Cited by 109 publications

(124 citation statements)

References 74 publications

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“…19) for 24 h. As shown in Fig. 2A, we found that steady-state levels of Ifi202 mRNA were relatively low in male mice than female mice ( Fig.…”

Section: Stimulation Of Splenic T Cells Up-regulates Ifi202 Expressionmentioning

confidence: 66%

“…Activation of c-Jun N-terminal kinase (JNK), which is also known as stress-activated protein kinase, is an important downstream event after T cell receptor (TCR) stimulation [18][19][20]. The JNK family belongs to the mitogen-activated protein kinase (MAPK) super families, which also includes the ERK and p38 families [19].…”

Section: Introductionmentioning

confidence: 99%

“…JNK phosphorylates the transcription factor c-Jun and increases the transcriptional activity of AP-1 [19,23]. Signals from both the TCR-CD3 complex and CD28 are required for JNK and AP-1 activation in T cells, and these signals may be integrated in a such a way as to mediate T cell activation and the induction of IL-2 transcription [19].…”

Section: Introductionmentioning

confidence: 99%

“…Signals from both the TCR-CD3 complex and CD28 are required for JNK and AP-1 activation in T cells, and these signals may be integrated in a such a way as to mediate T cell activation and the induction of IL-2 transcription [19]. Moreover, AP-1 has also been reported to be important for the regulation of Th1 and Th2 cytokine genes [19,24].…”

Section: Introductionmentioning

confidence: 99%

“…The JNK family belongs to the mitogen-activated protein kinase (MAPK) super families, which also includes the ERK and p38 families [19]. In T-cells, JNK is implicated in the integration of TCR and CD28 signals, which may play a role in T-cell activation and interleukin-2 production [18].…”

Section: Introductionmentioning

confidence: 99%

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Stimulation of T cells up-regulates expression of Ifi202, an interferon-inducible lupus susceptibility gene, through activation of JNK/c-Jun pathway

2008

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Studies have revealed that increased expression of interferon (IFN)-inducible Ifi202 gene (encoding p202 protein) in splenic B and T cells from B6.Nba2 congenic (congenic for Nb2 locus derived from NZB mice) female mice is associated with lupus susceptibility. However, signaling pathways that regulate Ifi202 expression in immune cells remain to be elucidated. Here we report that stimulation of T cells up-regulates the Ifi202 expression. We found that steady-state levels of Ifi202 mRNA and protein were detectable in splenic T cells from NZB mice and stimulation of T cells with anti-CD3

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“…19) for 24 h. As shown in Fig. 2A, we found that steady-state levels of Ifi202 mRNA were relatively low in male mice than female mice ( Fig.…”

Section: Stimulation Of Splenic T Cells Up-regulates Ifi202 Expressionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Stimulation of T cells up-regulates expression of Ifi202, an interferon-inducible lupus susceptibility gene, through activation of JNK/c-Jun pathway

2008

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MAPK/ERK and PI3K/AKT signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia

Loureiro,

Bahia,

Lee

et al. 2023

Cancer Reports

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Background: The mitogen‐activated protein kinase (MAPK)/ERK signaling cascade and the phosphoinosytol‐3 phosphate/Akt (PI3K/Akt) pathways are involved in proliferation and differentiation of hematopoietic cells. The frequency of PI3K/Akt and MAPK pathway activation in adult acute lymphoblastic leukemia (ALL) still need to be elucidated.Aims: To assess the activity and prognostic implications of MAPK/ERK and PI3K/Akt pathways in adult (ALL).MethodsWe examined 28 precursor‐B‐cell ALL and 6 T‐cell primary ALL samples. Flow cytometry was employed to analyze the expression levels of phosphorylated ERK and phosphorylated Akt.ResultsTen out of 15 (67%) ALL fresh samples (7 B‐cell, 3 T‐cell) showed constitutive p‐ERK expression. The p‐ERK mean fluorescent index ratio (MFI (R)) showed a tendency to be higher in ALL than in normal T lymphocytes (1.26 [0.74–3.10] vs. 1.08 [1.02–1.21], respectively [p = .069]) and was significantly lower than in leukemic cell lines (median MFI (R) 3.83 [3.71–5.97] [p < .001]). Expression of p‐Akt was found in 35% (12/34) (10 B‐cell, 2 T‐cell). The median MFI (R) expression for p‐Akt in primary blast cell was 1.13 (0.48–9.90) compared to 1.01 (1.00–1.20) in normal T lymphocytes (p = ns) and lower than in leukemic cell lines (median MFI (R) 2.10 [1.77–3.40] [p = .037]). Moreover, expression of p‐ERK was negatively associated with the expression of CD34 (1.22 [0.74–1.33] vs. 1.52 [1.15–3.10] for CD34(+) and CD34(−) group, respectively, p = .009).ConclusionOur findings suggest that both MAPK/ERK and PI3K/Akt are constitutively activated in adult ALL, indicating a targeted therapy potential for ALL by using inhibitors of these pathways.

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TCR ligand avidity determines the modeof B‐Raf/Raf‐1/ERK activation leading to the activationof human CD4⁺ T cell clone

et al. 2006

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The interactions between peptide/MHC complexes and their cognate TCR are essential for various T cell responses. However, the relationship between the avidity of TCR ligand and the subsequent intracellular signaling through the TCR is still unclear. To investigate the effects of TCR ligand avidity on TCR-mediated signaling, we established L cells expressing HLA-DR4 molecules covalently linked with agonistic peptide (highaffinity ligand) or altered peptide ligand (APL; low-affinity ligand) at various densities as APC for a cognate human CD4 + T cell clone. Using this system, we demonstrated that the T cell clone stimulated with APL/HLA-DR4 complexes presented at an excessive density provoked the up-regulation of CD69, IL-2 production and proliferation, but no detectable phosphorylation of ZAP-70/LAT/SLP-76. Furthermore, in contrast to the high-affinity stimulation, the low-affinity stimulation evoked delayed and sustained activation of the B-Raf/extracellular signal-regulated kinase (ERK) pathway without Raf-1 activation. The strength and duration of B-Raf/ERK activations closely correlated with the density of the TCR ligand. A knockdown approach confirmed that B-Raf activation was indispensable for the APL-induced T cell responses. These observations suggest that the differences in TCR-peptide/MHC interactions reflect the strength and duration of B-Raf/Raf-1/ERK activation in the human CD4 + T cells.

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Signal transduction by MAP kinases in T lymphocytes

Cited by 109 publications

References 74 publications

Stimulation of T cells up-regulates expression of Ifi202, an interferon-inducible lupus susceptibility gene, through activation of JNK/c-Jun pathway

Stimulation of T cells up-regulates expression of Ifi202, an interferon-inducible lupus susceptibility gene, through activation of JNK/c-Jun pathway

MAPK/ERK and PI3K/AKT signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia

TCR ligand avidity determines the modeof B‐Raf/Raf‐1/ERK activation leading to the activationof human CD4⁺ T cell clone

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Signal transduction by MAP kinases in T lymphocytes

Cited by 109 publications

References 74 publications

Stimulation of T cells up-regulates expression of Ifi202, an interferon-inducible lupus susceptibility gene, through activation of JNK/c-Jun pathway

Stimulation of T cells up-regulates expression of Ifi202, an interferon-inducible lupus susceptibility gene, through activation of JNK/c-Jun pathway

MAPK/ERK and PI3K/AKT signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia

TCR ligand avidity determines the modeof B‐Raf/Raf‐1/ERK activation leading to the activationof human CD4+ T cell clone

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Resources

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TCR ligand avidity determines the modeof B‐Raf/Raf‐1/ERK activation leading to the activationof human CD4⁺ T cell clone