Activation of the Cooh-Terminal Src Kinase (Csk) by Camp-Dependent Protein Kinase Inhibits Signaling through the T Cell Receptor

Vang, Torkel; Torgersen, Knut Martin; Sundvold, Vibeke; Saxena, Manju; Levy, Finn Olav; Skålhegg, Bjørn Steen; Hansson, V.; Mustelin, Tomas; Taskén, Kjetil

doi:10.1084/jem.193.4.497

Cited by 289 publications

(304 citation statements)

References 38 publications

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“…A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 16 phosphorylation of Csk at S364 by PKA type I. Phosphorylation of Csk at S364 increases its stability and activity (phosphorylation of Lck at Y505) and consequently inactivates Lck [29,33,34]. Since the PKA type I was involved in the inhibition of TCR V9V2 by PGE 2 , we analyzed the Y505 phosphorylation status of Lck after  T cell activation in the presence of PGE 2 .…”

Section: Page 16 Of 35mentioning

confidence: 99%

PGE2 inhibits natural killer and γδ T cell cytotoxicity triggered by NKR and TCR through a cAMP-mediated PKA type I-dependent signaling

Martinet¹,

Jean²,

Dietrich³

et al. 2010

Biochemical Pharmacology

108

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inhibits Natural Killer and γδ T cell cytotoxicity triggered by NKR and TCR through a cAMPmediated PKA type I-dependent signaling. Biochemical Pharmacology, Elsevier, 2010, 80 (6) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Page 16 Of 35mentioning

confidence: 99%

PGE2 inhibits natural killer and γδ T cell cytotoxicity triggered by NKR and TCR through a cAMP-mediated PKA type I-dependent signaling

Martinet¹,

Jean²,

Dietrich³

et al. 2010

Biochemical Pharmacology

108

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“…In particular, elevation of intracellular cAMP in T lymphocytes has an inhibitory effect on proliferation and IL-2 production (9), and has been shown to affect early T cell activation events (10). In this study, we have investigated whether there is any relationship between the increase of intracellular cAMP and CD152 expression in human CD4 ϩ T lymphocytes.…”

mentioning

confidence: 99%

Cyclic Adenosine 5′-Monophosphate and Calcium Induce CD152 (CTLA-4) Up-Regulation in Resting CD4+ T Lymphocytes

Vendetti

Riccomi

Sacchi

et al. 2002

The Journal of Immunology

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The CTLA-4 (CD152) molecule is up-regulated upon T cell activation and proliferation, and plays a critical role in the inhibition of immune responses. We show in this study that cAMP induces up-regulation of CD152 in human CD4+ T lymphocytes. This effect occurs in the absence of the up-regulation of CD69 and CD25 activation markers and T cell proliferation. In addition, we found that the Ca2+ ionophore ionomycin also up-regulates CD152, and that the combination of a cAMP analog or cAMP inducers with ionomycin further enhances the expression of CD152 in resting CD4+ T lymphocytes. However, cyclosporin A, which inhibits Ca2+/calcineurin signaling pathway, fully prevented the ionomycin- but not the cAMP-induced up-regulation of CD152. The effects of cAMP and ionomycin involve increase of both CD152 mRNA transcripts, coding for the membrane and the soluble forms of CD152. Furthermore, we show that CD152 molecules are translocated to the membrane and are functional, as their engagement by specific mAbs prevented NF-κB activation by anti-CD3/CD28 stimulation. These findings demonstrate that at least two novel signal pathways regulate CTLA-4 gene expression and CD152 molecule up-regulation in human CD4+ T lymphocytes, in the absence of full T cell activation.

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“…2A). It is well known that the effects of cAMP in immune systems are mediated by activating PKA or exchange factor directly activated by cAMP (EPAC) (36,37). Therefore, we performed the experiment using PKA-or EPAC-specific cAMP analogs.…”

Section: Cgrp Upregulates Il-9 Production From Naive T Cells Via Its mentioning

confidence: 99%

Calcitonin Gene-Related Peptide and Cyclic Adenosine 5′-Monophosphate/Protein Kinase A Pathway Promote IL-9 Production in Th9 Differentiation Process

Mikami

Miyagi

Sueda

et al. 2013

The Journal of Immunology

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Th9 cells are a novel Th cell subset that produces IL-9 and is involved in type I hypersensitivity such as airway inflammation. Although its critical roles in asthma have attracted interest, the physiological regulatory mechanisms of Th9 cell differentiation and function are largely unknown. Asthma is easily affected by psychological factors. Therefore, we investigated one of the physiological mediators derived from the nervous system, calcitonin gene-related peptide (CGRP), in asthma and Th9 cells because CGRP and activation of the cAMP/protein kinase A (PKA) pathway by CGRP are known to be important regulators in several immune responses and allergic diseases. In this study, we demonstrated that the CGRP/cAMP/PKA pathway promotes IL-9 production via NFATc2 activation by PKA-dependent glycogen synthase kinase-3β inactivation. Moreover, CGRP also induces the expression of PU.1, a critical transcriptional factor in Th9 cells, which depends on PKA, but not NFATc2. Additionally, we demonstrated the physiological importance of CGRP in IL-9 production and Th9 differentiation using an OVA-induced airway inflammation model and T cell–specific CGRP receptor-deficient mice. The present study revealed a novel regulatory mechanism comprising G protein–coupled receptor ligands and nervous system-derived substances in Th9 cell differentiation and type I hypersensitivity.

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Activation of the Cooh-Terminal Src Kinase (Csk) by Camp-Dependent Protein Kinase Inhibits Signaling through the T Cell Receptor

Cited by 289 publications

References 38 publications

PGE2 inhibits natural killer and γδ T cell cytotoxicity triggered by NKR and TCR through a cAMP-mediated PKA type I-dependent signaling

PGE2 inhibits natural killer and γδ T cell cytotoxicity triggered by NKR and TCR through a cAMP-mediated PKA type I-dependent signaling

Cyclic Adenosine 5′-Monophosphate and Calcium Induce CD152 (CTLA-4) Up-Regulation in Resting CD4+ T Lymphocytes

Calcitonin Gene-Related Peptide and Cyclic Adenosine 5′-Monophosphate/Protein Kinase A Pathway Promote IL-9 Production in Th9 Differentiation Process

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