c-Jun N-terminal Kinase but Not Mitogen-activated Protein Kinase Is Sensitive to cAMP Inhibition in T Lymphocytes (*)

The molecular mechanism underlying the cAMP inhibition of nuclear activation events in T lymphocytes is unknown. Recently, the activation of fibroblasts and muscle cells are shown to be antagonized by cAMP through the inhibition of mitogen-activated protein (MAP) kinases signaling pathway. Whether a similar antagonism may account for the late inhibitory effect of cAMP in T cell was examined. Surprisingly, extracellular signal regulated kinase 2 (ERK2) activation was resistant to cAMP inhibition in all the T lymphocytes tested. Different isoforms (ERK1, ERK2, and ERK3) of MAP kinase were poorly inhibited by cAMP. High concentration of cAMP also only weakly antagonized Raf-1 in T cells. The resistance of ERK and Raf-1 to cAMP clearly distinguishes T cells from fibroblasts. In contrast, another MAP kinase homologue c-Jun N-terminal kinase (JNK) was inhibited by cAMP in good correlation with that of IL-2 suppression. Moreover, JNK was antagonized by a delayed kinetics which is characteristic of cAMP inhibition. Despite that both ERK and JNK are essential for T cell activation, selective inhibition by cAMP further supports the specific role of JNK in T cell activation.

• Publication year

  1995

• Venue

  Journal of Biological Chemistry

• Publication date

  1995-07-28

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.270.30.18094PMID 7629120
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• JNK is involved in signal integration during costimulation of T lymphocytes.

  1994cited by this paper
• JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain.

  1994cited by this paper
• cAMP abrogates the p21ras-mitogen-activated protein kinase pathway in fibroblasts.

  1994cited by this paper
• B-Raf-dependent regulation of the MEK-1/mitogen-activated protein kinase pathway in PC12 cells and regulation by cyclic AMP

  1994cited by this paper
• Mechanism of inhibition of Raf-1 by protein kinase A

  1994cited by this paper
• Mitogen-activated protein (MAP) kinase phosphorylation of MAP kinase kinase: determination of phosphorylation sites by mass spectrometry and site-directed mutagenesis.

  1994cited by this paper
• The role of Raf-1 in the regulation of extracellular signal-regulated kinase 2 by the T cell antigen receptor

  1994cited by this paper
• The stress-activated protein kinase subfamily of c-Jun kinases

  1994cited by this paper
• Interleukin 2 transcription factors as molecular targets of cAMP inhibition: delayed inhibition kinetics and combinatorial transcription roles

  1994cited by this paper
• Enzymatic characteristics of the c-Raf-1 protein kinase.

  1994cited by this paper
• The native structure of the activated Raf protein kinase is a membrane-bound multi-subunit complex.

  1994cited by this paper
• Signal transduction by lymphocyte antigen receptors.

  1994cited by this paper
• Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK.

  1994cited by this paper
• Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1

  1994cited by this paper
• Sequential protein kinase reactions controlling cell growth and differentiation.

  1994cited by this paper
• An osmosensing signal transduction pathway in mammalian cells.

  1994cited by this paper
• Increasing cAMP attenuates activation of mitogen-activated protein kinase.

  1993cited by this paper
• cAMP antagonizes p21ras‐directed activation of extracellular signal‐regulated kinase 2 and phosphorylation of mSos nucleotide exchange factor.

  1993cited by this paper
• Inhibition of the EGF-activated MAP kinase signaling pathway by adenosine 3',5'-monophosphate.

  1993cited by this paper
• Protein kinase A antagonizes platelet-derived growth factor-induced signaling by mitogen-activated protein kinase in human arterial smooth muscle cells.

  1993cited by this paper
• Overexpression of mitogen-activated protein kinase (ERK1) enhances T-cell cytokine gene expression: role of AP1, NF-AT, and NF-KB.

  1993cited by this paper
• Inhibition by cAMP of Ras-dependent activation of Raf.

  1993cited by this paper
• Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain.

  1993cited by this paper
• cAMP analogs prevent activation-induced apoptosis of T cell hybridomas.

  1993cited by this paper
• NF-kappa B activation by ultraviolet light not dependent on a nuclear signal.

  1993cited by this paper
• Raf‐1 is required for T cell IL2 production.

  1993cited by this paper
• Prostaglandin E2 and other cyclic AMP-elevating agents modulate IL-2 and IL-2R alpha gene expression at multiple levels.

  1992cited by this paper
• Activation of extracellular signal‐regulated kinase, ERK2, by p21ras oncoprotein.

  1992cited by this paper
• The regulation and function of p21ras in T cells.

  1992cited by this paper
• Extracellular signal-regulated kinases in T cells. Anti-CD3 and 4 beta-phorbol 12-myristate 13-acetate-induced phosphorylation and activation.

  1992cited by this paper
• Interleukin-2-triggered Raf-1 expression, phosphorylation, and associated kinase activity increase through G1 and S in CD3-stimulated primary human T cells

  1991cited by this paper
• Activation of messenger-independent protein kinases in wild-type and phorbol ester-resistant EL4 thymoma cells.

  1991cited by this paper
• Stimulation of MAP-2 kinase activity in T lymphocytes by anti-CD3 or anti-Ti monoclonal antibody is partially dependent on protein kinase C.

  1990cited by this paper
• The adenylate cyclase-cAMP-protein kinase A pathway and regulation of the immune response.

  1988cited by this paper
• Cyclic AMP concentrations modulate both calcium flux and hydrolysis of phosphatidylinositol phosphates in mouse T lymphocytes.

  1988cited by this paper
• T cell receptor gene usage in the response to lambda repressor cI protein. An apparent bias in the usage of a V alpha gene element

  1988cited by this paper
• Aluminum fluoride induces phosphatidylinositol turnover, elevation of cytoplasmic free calcium, and phosphorylation of the T cell antigen receptor in murine T cells.

  1987cited by this paper
• Regulation of interleukin 2 synthesis by cAMP in human T cells.

  1987cited by this paper
• T lymphocyte response to bacteriophage lambda repressor cI protein. Recognition of the same peptide presented by Ia molecules of different haplotypes.

  1987cited by this paper

• GPER deletion triggers inhibitory effects in triple negative breast cancer (TNBC) cells through the JNK/c-Jun/p53/Noxa transduction pathway

  2023cites this paper
• JNK suppresses melanogenesis by interfering with CREB-regulated transcription coactivator 3-dependent MITF expression

  2020cites this paper
• Metabolic disorder induces fatty liver in Japanese seabass, Lateolabrax japonicas fed a full plant protein diet and regulated by cAMP-JNK/NF-kB-caspase signal pathway.

  2019cites this paper
• (CREB) Binding Protein Interaction Induced AMP-Responsive Element Binding Protein Multiple Signals Required for Cyclic

  2013cites this paper
• cAMP-dependent Protein Kinase and c-Jun N-terminal Kinase Mediate Stathmin Phosphorylation for the Maintenance of Interphase Microtubules during Osmotic Stress*

  2013cites this paper
• Epac as a novel regulator of airway smooth muscle phenotype and function: potential implications in asthma and COPD

  2010cites this paper
• Selective induction of apoptosis via the TNF system in hepatocellular carcinoma

  2009cites this paper
• Selective induction of apoptosis via the TNF system in hepatocellular carcinoma

  2009cites this paper
• GENERATION AND CHARACTERIZATION OF THE CELLULAR IMMUNE RESPONSE TO A CLOSTRIDIUM PERFRINGENS ANTI-SIV MUCOSAL VACCINE

  2008cites this paper
• Relations between the mitogen-activated protein kinase and the cAMP-dependent protein kinase pathways: comradeship and hostility.

  2008cites this paper
• cAMP Modulates Macrophage Development by Suppressing M-CSF-Induced MAPKs Activation

  2008cites this paper
• Pharmacology of airway smooth muscle proliferation.

  2008cites this paper
• Cyclic AMP inhibits JNK activation by CREB-mediated induction of c-FLIPL and MKP-1, thereby antagonizing UV-induced apoptosis

  2008cites this paper
• Expression and regulation of mRNA for distinct isoforms of cAMP-specific PDE-4 in mitogen-stimulated and leukemic human lymphocytes

  2007cites this paper
• Isoproterenol suppresses cytokine-induced RANTES secretion in human lung epithelial cells through the inhibition of c-jun N-terminal kinase pathway.

  2006cites this paper
• Cyclic AMP Inhibits p38 Activation via CREB-Induced Dynein Light Chain

  2006cites this paper
• Failure of catecholamines to shift T-cell cytokine responses toward a Th2 profile in patients with rheumatoid arthritis

  2006cites this paper
• Mitochondrial Signal Transduction Abnormalities in Systemic Lupus Erythematosus

  2005cites this paper
• Beta2-Adrenergic Receptors Mediate the Differential Effects of Catecholamines on Cytokine Production of PBMC

  2005cites this paper
• PDE4 inhibitors as new anti-inflammatory drugs: effects on cell trafficking and cell adhesion molecules expression.

  2005cites this paper
• Selective modulation of lipopolysaccharide-stimulated cytokine expression and mitogen-activated protein kinase pathways by dibutyryl-cAMP in BV2 microglial cells.

  2003cites this paper
• Downregulation of p38 kinase pathway by cAMP response element-binding protein protects HL-60 cells from iron chelator-induced apoptosis.

  2003cites this paper
• T Lymphocytes + Activation of Human CD 4 Extracellular Adenine Nucleotides Inhibit the Boeynaems and Didier Communi

  2002cites this paper
• Mitogen-activated protein kinases and their role in regulation of cellular processes.

  2002cites this paper
• Extracellular Adenine Nucleotides Inhibit the Activation of Human CD4+ T Lymphocytes1

  2002cites this paper
• Ketoconazole suppresses prostaglandin E(2)-induced cyclooxygenase-2 expression in human epidermoid carcinoma A-431 cells.

  2002cites this paper
• Crosstalk between cAMP and MAP kinase signaling in the regulation of cell proliferation.

  2002cites this paper
• Cardiac function and electrical remodeling of the calcineurin-overexpressed transgenic mouse.

  2002cites this paper
• Signal transduction pathways and apoptosis in bacteria infected chondrocytes

  2001cites this paper
• Dependent Protein Kinase A Human T Lymphocytes Is Not Mediated by ( cAMP )-Dependent Inhibition of IL-5 from-Cyclic Monophosphate ′ , 5 ′ Adenosine 3

  2001cites this paper
• Downregulation of Phospholipase C δ3 by cAMP and Calcium

  2001cites this paper
• Stimulation of human extravillous trophoblast migration by IGF-II is mediated by IGF type 2 receptor involving inhibitory G protein(s) and phosphorylation of MAPK.

  2001cites this paper
• Downregulation of phospholipase C delta3 by cAMP and calcium.

  2001cites this paper
• cAMP potentiates H(2)O(2)-induced ERK1/2 phosphorylation without the requirement for MEK1/2 phosphorylation.

  2001cites this paper
• Protein Kinase A RIβ Subunit Deficiency in Lupus T Lymphocytes: Bypassing a Block in RIβ Translation Reconstitutes Protein Kinase A Activity and Augments IL-2 Production1

  2001cites this paper
• Protein Kinase A RIb Subunit Deficiency in Lupus T Lymphocytes: Bypassing a Block in RI b Translation Reconstitutes Protein Kinase A Activity and Augments IL-2 Production

  2001cites this paper
• Beta2-adrenergic receptor/cyclic adenosine monophosphate (cAMP) leads to JNK activation through Rho family small GTPases.

  2001cites this paper
• Multiple Signals Required for Cyclic AMP-Responsive Element Binding Protein (CREB) Binding Protein Interaction Induced by CD3/CD28 Costimulation1

  2001cites this paper
• Adenosine 3′,5′-Cyclic Monophosphate (cAMP)-Dependent Inhibition of IL-5 from Human T Lymphocytes Is Not Mediated by the cAMP-Dependent Protein Kinase A1

  2001cites this paper
• Mercuric chloride stimulates distinct signal transduction pathway for DNA synthesis in a T‐cell line, CTLL‐2

  2000cites this paper
• Immunosuppressive and anti-inflammatory effects of cyclic AMP phosphodiesterase (PDE) type 4 inhibitors.

  2000cites this paper
• Vasoactive intestinal peptide and pituitary adenylate cyclase activating polypeptide inhibit the MEKK1/MEK4/JNK signaling pathway in LPS-stimulated macrophages.

  2000cites this paper
• Glutamine metabolism stimulates intestinal cell MAPKs by a cAMP-inhibitable, Raf-independent mechanism.

  2000cites this paper
• Extracellular ATP as a Regulator of Intracellular Signaling in Thyroid FRTL-5 Cells

  2000cites this paper
• Gata-3 Induces T Helper Cell Type 2 (Th2) Cytokine Expression and Chromatin Remodeling in Committed Th1 Cells

  2000cites this paper
• Cyclic AMP Activates p38 Mitogen-Activated Protein Kinase in Th2 Cells: Phosphorylation of GATA-3 and Stimulation of Th2 Cytokine Gene Expression1

  2000cites this paper
• Integration of Calcium and Cyclic AMP Signaling Pathways by 14-3-3

  2000cites this paper
• Plunkett Nucleoside Analogue-induced DNA Damage The Role of c-jun Kinase in the Apoptotic Response to Updated

  2000cites this paper
• Receptors and Transcriptional Factors Involved in the Anti‐Inflammatory Activity of VIP and PACAP

  2000cites this paper
• The role of c-Jun kinase in the apoptotic response to nucleoside analogue-induced DNA damage.

  2000cites this paper
• Gene Expression of GATA-3 and Stimulation of Th 2 Cytokine PhosphorylationProtein Kinase in Th 2 Cells : Cyclic AMP Activates p 38 Mitogen-Activated

  2000cites this paper
• Elevation of intracellular cAMP inhibits growth factor-mediated matrix metalloproteinase-9 induction and keratinocyte migration.

  2000influential citation
• Somatostatin analog SMS 201995 inhibits proliferation in human leukemia T‐cell line: Relevance of the adenylyl cyclase stimulation

  2000cites this paper
• Cyclic AMP regulates cell size of Schizosaccharomyces pombe through Cdc25 mitotic inducer

  2000cites this paper
• The neuropeptides VIP and PACAP inhibit IL-2 transcription by decreasing c-Jun and increasing JunB expression in T cells.

  2000cites this paper
• Suppression of T cell function: a potential role for transcriptional repressor ICER

  2000cites this paper
• Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide enhance IL-10 production by murine macrophages: in vitro and in vivo studies.

  1999cites this paper
• Macrophages : In Vitro and In Vivo Studies Enhance IL-10 Production by Murine Adenylate Cyclase-Activating Polypeptide Vasoactive Intestinal Peptide and Pituitary and Doina Ganea

  1999cites this paper
• A Novel Regulatory Mechanism of Map Kinases Activation and Nuclear Translocation Mediated by Pka and the Ptp-Sl Tyrosine Phosphatase

  1999cites this paper
• Cyclic AMP suppresses interleukin‐5 synthesis by human helper T cells via the downregulation of the calcium mobilization pathway

  1999cites this paper
• Cyclic nucleotide phosphodiesterases (PDE) 3 and 4 in normal, malignant, and HTLV-I transformed human lymphocytes.

  1999cites this paper
• Diminished levels of protein kinase A RI alpha and RI beta transcripts and proteins in systemic lupus erythematosus T lymphocytes.

  1999cites this paper
• Effects of dehydroepiandrosterone on mitogen-activated protein kinase in human aortic smooth muscle cells.

  1999cites this paper
• Inflammation and lipid-lowering treatment

  1999cites this paper
• NF-kappa B-dependent Fas ligand expression.

  1999cites this paper
• Cyclic AMP inhibits the activity of c-Jun N-terminal kinase (JNKp46) but not JNKp55 and ERK2 in human helper T lymphocytes.

  1999cites this paper
• Vasoactive intestinal peptide inhibits cytokine production in T lymphocytes through cAMP-dependent and cAMP-independent mechanisms.

  1999cites this paper
• Differential Activation of Mitogen‐Activated Protein Kinase Pathways in PC12 Cells by Closely Related α1‐Adrenergic Receptor Subtypes

  1999cites this paper
• CD3- and CD28-dependent induction of PDE7 required for T cell activation.

  1999cites this paper
• Advances in the signal transduction of ceramide and related sphingolipids.

  1999cites this paper
• VIP and PACAP38 Modulate Cytokine and Nitric Oxide Production in Peritoneal Macrophages and Macrophage Cell Lines

  1999cites this paper
• Multiple levels of regulation of Th2 cytokine gene expression.

  1999cites this paper
• p38 Mitogen-activated Protein Kinase Is Involved in Fas Ligand Expression*

  1999cites this paper
• Transmodulation of Epidermal Growth Factor Receptor Function by Cyclic AMP-dependent Protein Kinase*

  1999cites this paper
• Diminished Levels of Protein Kinase A RIα and RIβ Transcripts and Proteins in Systemic Lupus Erythematosus T Lymphocytes

  1999cites this paper
• NF‐κB‐dependent Fas ligand expression

  1999cites this paper
• Lupus T Lymphocytes Transcripts and Proteins in Systemic b and RI a Diminished Levels of Protein Kinase A RI

  1999cites this paper
• Differential activation of mitogen-activated protein kinase pathways in PC12 cells by closely related alpha1-adrenergic receptor subtypes.

  1999cites this paper
• A Novel Regulatory Mechanism of Map Kinases Activation and Nuclear Translocation Mediated by Pka and the Ptp-sl Tyrosine Phosphatase

  1999cites this paper
• Atypical signaling defects prevent IL-2 gene expression in lpr/lpr CD4-CD8- cells.

  1998cites this paper
• Mitogen-activated Protein Kinase Kinase Antagonized Fas-associated Death Domain Protein–mediated Apoptosis by Induced FLICE-inhibitory Protein Expression

  1998cites this paper
• Hyperosmotic induction of the mitogen-activated protein kinase phosphatase MKP-1 in H4IIE rat hepatoma cells.

  1998cites this paper
• Coordinate Transactivation of the Interleukin-2 CD28 Response Element by c-Rel and ATF-1/CREB2*

  1998cites this paper
• Regulation of the cAMP cascade, gene expression and immune function by cannabinoid receptors.

  1998cites this paper
• Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-activating Polypeptide Inhibit Tumor Necrosis Factor α Transcriptional Activation by Regulating Nuclear Factor-kB and cAMP Response Element-binding Protein/c-Jun*

  1998cites this paper
• Role of Transcriptional Repressor ICER in Cyclic AMP-mediated Attenuation of Cytokine Gene Expression in Human Thymocytes*

  1998cites this paper
• The role of mitogen-activated protein kinases in Listeria monocytogenes invasion

  1998cites this paper
• CD2 signalling induces phosphorylation of CREB in primary lymphocytes

  1998cites this paper
• Co-stimulation of human peripheral blood mononuclear cells with IL-2 and anti-CD3 monoclonal antibodies induces phosphorylation of CREB.

  1998cites this paper
• Interleukin-4 overcomes the negative influence of cyclic AMP accumulation on antigen receptor stimulated B lymphocytes.

  1998cites this paper
• Inhibition of the cAMP signaling cascade via cannabinoid receptors: a putative mechanism of immune modulation by cannabinoid compounds.

  1998cites this paper
• Apoptotic signal of Fas is not mediated by ceramide.

  1998cites this paper
• Prostaglandin E2 differentially modulates IL-5 gene expression in activated human T lymphocytes depending on the costimulatory signal.

  1998cites this paper
• Compatible Organic Osmolytes and Osmotic Modulation of Inducible Nitric Oxide Synthetase in RAW 264.7 Mouse Macrophages

  1998cites this paper
• Growth factor-induced transcription via the serum response element is inhibited by cyclic adenosine 3',5'-monophosphate in MCF-7 breast cancer cells.

  1997cites this paper
• Comparison Between the Timing of JNK activation, c‐Jun Phosphorylation, and Onset of Death Commitment in Sympathetic Neurones

  1997cites this paper
• Vasoactive intestinal peptide stimulates p59fyn kinase activity in murine thymocytes.

  1997cites this paper
• The effect of tumor necrosis factor-alpha and cAMP on induction of AP-1 activity in MA-10 tumor Leydig cells.

  1997cites this paper
• Effect of vasoactive intestinal peptide (VIP) on cytokine production and expression of VIP receptors in thymocyte subsets.

  1997cites this paper
• Differential expression of cyclic nucleotide phosphodiesterase 3 and 4 activities in human T cell clones specific for myelin basic protein.

  1997cites this paper