Activation of Mitogen-activated Protein Kinase by Arachidonic Acid in Rat Liver Epithelial WB Cells by a Protein Kinase C-dependent Mechanism (*)

Arachidonic acid (20:4(n-6)), which is released by cells responding to a wide range of stimuli, may play an important role in intracellular signaling. We now report that incubation of WB cells with 20:4(n-6) resulted in the appearance of several tyrosine-phosphorylated cytosolic proteins. Two of the phosphotyrosine-containing proteins, migrating in SDS-polyacrylamide gels of approximately 43 and 45 kDa, corresponded in mobility to phosphorylated species of the 42- and 44-kDa mitogen-activated protein kinase (MAPK) isoforms. Immunoblots of soluble fractions from unstimulated WB cells with anti-MAPK antibodies revealed the presence of the 42- and 44-kDa isoforms of MAPK. Upon incubation with 20:4(n-6), the mobility of both isoforms was retarded, consistent with their activation by phosphorylation. Chromatography of soluble fractions from these cells on Mono Q columns revealed early and late eluting peaks of myelin basic protein kinase activity, which contained the 42- and 44-kDa MAPK isoforms, respectively. Activation of MAPK was transient, peaking at 5 min, and was detectable at 5 μM 20:4(n-6). Further studies into the mechanisms by which MAPK was activated by 20:4(n-6) strongly suggested the involvement of protein kinase C (PKC). Not only did incubation of WB cells with 20:4(n-6) result in the translocation of PKC α, δ, and ϵ to a particulate fraction, it was found that the fatty acid failed to activate MAPK in cells pretreated for 26 h with phorbol 12-myristate 13-acetate, which depleted WB cells of PKC α, δ, and ϵ. In addition, fatty acids of the n-3 series were effective activators of MAPK. The present study, to our knowledge, is the first to report that polyunsaturated fatty acids can cause the activation of MAPK.

• Publication year

  1995

• Venue

  Journal of Biological Chemistry

• Publication date

  1995-03-03

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.270.9.4201PMID 7876176
• 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.

• A tyrosine phosphorylation requirement for cytotoxic T lymphocyte degranulation.

  1994cited by this paper
• Binding of 14-3-3 proteins to the protein kinase Raf and effects on its activation.

  1994cited by this paper
• Lysophosphatidic acid inhibits gap-junctional communication and stimulates phosphorylation of connexin-43 in WB cells: possible involvement of the mitogen-activated protein kinase cascade.

  1994cited by this paper
• Neutrophil migration inhibitory properties of polyunsaturated fatty acids. The role of fatty acid structure, metabolism, and possible second messenger systems.

  1994cited by this paper
• MAP kinase kinase kinase, MAP kinase kinase and MAP kinase.

  1994cited by this paper
• Identification, partial purification, and characterization of a novel phospholipid-dependent and fatty acid-activated protein kinase from human platelets.

  1994cited by this paper
• Identification of arachidonic acid as a mediator of sphingomyelin hydrolysis in response to tumor necrosis factor alpha.

  1994cited by this paper
• Differential Raf requirement for activation of mitogen-activated protein kinase by growth factors, phorbol esters, and calcium.

  1994cited by this paper
• In Vitro Activation of Rat Brain Protein Kinase C by Polyenoic Very‐Long‐Chain Fatty Acids

  1994cited by this paper
• Stimulatory effects of yeast and mammalian 14-3-3 proteins on the Raf protein kinase.

  1994cited by this paper
• RAS is required for epidermal growth factor-stimulated arachidonic acid release in rat-1 fibroblasts.

  1993cited by this paper
• Regulation of gene transcription by polyunsaturated fatty acids.

  1993cited by this paper
• cPLA2 is phosphorylated and activated by MAP kinase.

  1993cited by this paper
• Protein kinase Cα activates RAF-1 by direct phosphorylation

  1993cited by this paper
• Epidermal growth factor-induced actin remodeling is regulated by 5-lipoxygenase and cyclooxygenase products.

  1993cited by this paper
• Activation of myelin basic protein and S6 peptide kinases in phorbol ester- and PAF-treated sheep platelets.

  1993cited by this paper
• Reconstitution of the Raf-1—MEK—ERK Signal Transduction Pathway In Vitro

  1993cited by this paper
• Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor.

  1993cited by this paper
• Protein kinase C alpha activates RAF-1 by direct phosphorylation.

  1993cited by this paper
• Polyunsaturated fatty acids increase neutrophil adherence and integrin receptor expression

  1993cited by this paper
• A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf

  1993cited by this paper
• Essential fatty acids and eicosanoids

  1993cited by this paper
• The protein kinase C family.

  1992cited by this paper
• Arachidonic acid-induced insulin secretion from rat islets of Langerhans.

  1992cited by this paper
• ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK.

  1992cited by this paper
• Long-chain fatty acids activate calcium channels in ventricular myocytes.

  1992cited by this paper
• Arachidonic acid as a second messenger. Interactions with a GTP-binding protein of human neutrophils.

  1991cited by this paper
• The GTPase stimulatory activities of the neurofibromatosis type 1 and the yeast IRA2 proteins are inhibited by arachidonic acid.

  1991cited by this paper
• Polyunsaturated free fatty acids stimulate an increase in cytosolic Ca2+ by mobilizing the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool in T cells through a mechanism independent of phosphoinositide turnover.

  1990cited by this paper
• Effect of propranolol on accumulation of NEFA in the ischemic perfused rat heart.

  1989cited by this paper
• Influence of lipids on gap-junction-mediated intercellular communication between Chinese hamster cells in vitro.

  1986cited by this paper
• Intracellular Ca2+ mobilization by arachidonic acid. Comparison with myo-inositol 1,4,5-trisphosphate in isolated pancreatic islets.

  1986cited by this paper
• cis-Polyunsaturated fatty acids induce high levels of superoxide production by human neutrophils.

  1981cited by this paper

• Transcriptomic profiling of phospholipase A2 and the role of arachidonic acid during Brucella abortus 544 infection in both in vitro and in vivo systems.

  2020cites this paper
• Supervised machine learning models and protein-protein interaction network analysis of gene expression profiles induced by omega-3 polyunsaturated fatty acids

  2020cites this paper
• Beneficial Effect of Long-Chain Omega-3 Fatty Acids in Psoriasis

  2016cites this paper
• Protein Kinase Cα Regulates the Expression of Complement Receptor Ig in Human Monocyte–Derived Macrophages

  2015cites this paper
• Production and purification of recombinant hypocholesterolemic peptides

  2014cites this paper
• p38 mitogen-activated protein kinase interacts with vinculin at focal adhesions during fatty acid-stimulated cell adhesion.

  2013cites this paper
• Omega-3 fatty acids as pharmacotherapeutics in psoriasis: current status and scope of nanomedicine in its effective delivery.

  2013cites this paper
• Regulation of Neutrophil Functions by Long Chain Fatty Acids

  2013cites this paper
• Signaling Pathways Involved in the Effects of Different Fatty Acids on Interleukin-2 Induced Human Lymphocyte Proliferation

  2013cites this paper
• Arachidonic acid stimulates DNA synthesis in brown preadipocytes through the activation of protein kinase C and MAPK.

  2012cites this paper
• Arachidonic acid and its COX1/2 metabolites inhibit interferon-γ mediated induction of indoleamine-2,3 dioxygenase in THP-1 cells and human monocytes.

  2012cites this paper
• Regulation of CRIg expression and phagocytosis in human macrophages by arachidonate, dexamethasone, and cytokines.

  2011cites this paper
• The pharmacology and activity of non-steroidal anti-inflammatory drugs (NSAIDs): a review of their use as an adjuvant treatment in patients with HBV and HCV chronic hepatitis

  2011cites this paper
• Regulatory activity of polyunsaturated fatty acids in T-cell signaling.

  2010cites this paper
• EFECTO DE LA DIETA EN EL NIVEL DE EXPRESIÓN GÉNICA DE LAS ENZIMAS ACETIL-COA CARBOXILASA, LIPOPROTEIN LIPASA Y ESTEAROIL-COA DESATURASA, ENZIMAS LIPOGÉNICAS IMPLICADAS EN LA SÍNTESIS Y ACUMULACIÓN DE ÁCIDOS GRASOS INSATURADOS EN EL DEPÓSITO

  2010cites this paper
• Polyunsaturated fatty acids in the modulation of T-cell signalling.

  2010cites this paper
• A role for the phosphatidylinositol 3-kinase--protein kinase C zeta--Sp1 pathway in the 1,25-dihydroxyvitamin D3 induction of the 25-hydroxyvitamin D3 24-hydroxylase gene in human kidney cells.

  2010cites this paper
• The arachidonic acid effect on platelet nitric oxide level.

  2009cites this paper
• The Effect of Mutations in Stearoyl CoA Desaturase Gene and Fatty Acid Synthase on Milk Composition and Fatty Acid Profile in Milk Fat of Dairy Cows

  2009cites this paper
• Effect of 5‐lipoxygenase inhibitor MK591 on early molecular and signaling events induced by staphylococcal enterotoxin B in human peripheral blood mononuclear cells

  2008cites this paper
• Non-dioxin-like polychlorinated biphenyls induce a release of arachidonic acid in liver epithelial cells: a partial role of cytosolic phospholipase A(2) and extracellular signal-regulated kinases 1/2 signalling.

  2008influential citation
• Regulation of the NADPH oxidase activity and anti-microbial function of neutrophils by arachidonic acid

  2007cites this paper
• Arachidonic acid inhibits osteoblast differentiation through cytosolic phospholipase A2-dependent pathway.

  2007cites this paper
• Novel action of n-3 polyunsaturated fatty acids: inhibition of arachidonic acid-induced increase in tumor necrosis factor receptor expression on neutrophils and a role for proteases.

  2007cites this paper
• Oxidative modulation of transient potassium current by arachidonic acid in brain central neurons

  2007cites this paper
• Molecular mechanism of methyl jasmonate induced apoptosis in human cancer cells

  2007cites this paper
• A novel regulatory pathway for cholesterol degradation via lactostatin.

  2007cites this paper
• A Novel β-Oxa Polyunsaturated Fatty Acid Downregulates the Activation of the I&kgr;B Kinase/Nuclear Factor &kgr;B Pathway, Inhibits Expression of Endothelial Cell Adhesion Molecules, and Depresses Inflammation

  2006cites this paper
• The positive feedback role of arachidonic acid in the platelet-derived growth factor-induced signaling in lens epithelial cells.

  2006cites this paper
• Oxygen radical generation by lymphoblast NADPH oxidase in hypertension

  2006cites this paper
• Evaluation of milk somatic cells as a source of mRNA for study of lipogenesis in the mammary gland of lactating beef cows supplemented with dietary high-linoleate safflower seeds.

  2006cites this paper
• A novel beta-oxa polyunsaturated fatty acid downregulates the activation of the IkappaB kinase/nuclear factor kappaB pathway, inhibits expression of endothelial cell adhesion molecules, and depresses inflammation.

  2006cites this paper
• Involvement of phospholipase A2 and lipoxygenase in lipopolysaccharide‐induced inducible nitric oxide synthase expression in glial cells

  2005cites this paper
• Arachidonic Acid Inhibits the Insulin Induction of Glucose-6-phosphate Dehydrogenase via p38 MAP Kinase*

  2005cites this paper
• Molecular action of 1,25-dihydroxyvitamin D3 and phorbol ester on the activation of the rat cytochrome P450C24 (CYP24) promoter: role of MAP kinase activities and identification of an important transcription factor binding site.

  2005cites this paper
• Long-chain polyunsaturated fatty acids protect the heart against ischemia/reperfusion-induced injury via a MAPK dependent pathway.

  2005cites this paper
• A possible signal transduction pathway for cyclin D2 expression by a pectic polysaccharide from the roots of bupleurum falcatum L. in murine B cell.

  2005cites this paper
• Investigation into the intracellular mechanisms whereby long-chain fatty acids protect the heart in ischaemia/reperfusion

  2005cites this paper
• Decrease of human hepatoma cell growth by arachidonic acid is associated with an accumulation of derived products from lipid peroxidation.

  2004cites this paper
• Anisomycin downregulates gap-junctional intercellular communication via the p38 MAP-kinase pathway

  2004influential citation
• Characterization of the MEK5-ERK5 Module in Human Neutrophils and Its Relationship to ERK1/ERK2 in the Chemotactic Response*

  2004cites this paper
• Arachidonic acid activates tissue transglutaminase and stress fiber formation via intracellular reactive oxygen species.

  2004cites this paper
• Over-expression of the mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPK in hepatocellular carcinoma: Its role in tumor progression and apoptosis

  2003cites this paper
• Role of p38 MAPK in CYP2E1-dependent Arachidonic Acid Toxicity*

  2003cites this paper
• Selective deficiency in protein kinase C isoenzyme expression and inadequacy in mitogen-activated protein kinase activation in cord blood T cells.

  2003cites this paper
• 2 Phospholipase A Extracellular Signal-Regulated Kinase, and Up-Regulation Involving Protein Kinase C, Neutrophil TNF Receptor Expression: Unique Effect of Arachidonic Acid on Human

  2003cites this paper
• Regulation of Epidermal Growth Factor-induced Connexin 43 Gap Junction Communication by Big Mitogen-activated Protein Kinase 1/ERK5 but Not ERK1/2 Kinase Activation*

  2003cites this paper
• Unique Effect of Arachidonic Acid on Human Neutrophil TNF Receptor Expression: Up-Regulation Involving Protein Kinase C, Extracellular Signal-Regulated Kinase, and Phospholipase A2 1

  2003cites this paper
• Cell type‐dependent activation of 5‐lipoxygenase by arachidonic acid

  2003cites this paper
• Extracellular signal‐regulated kinases phosphorylate 5lipoxygenase and stimulate 5‐lipoxygenase product formation in leukocytes

  2002cites this paper
• Induction of MnSOD gene by arachidonic acid is mediated by reactive oxygen species and p38 MAPK signaling pathway in human HepG2 hepatoma cells.

  2002cites this paper
• Eicosapentaenoic acid and docosahexaenoic acid modulate MAP kinase enzyme activity in human T-cells

  2002cites this paper
• The Mechanism of Docosahexaenoic Acid-induced Phospholipase D Activation in Human Lymphocytes Involves Exclusion of the Enzyme from Lipid Rafts*

  2002cites this paper
• Extracellular signal‐regulated kinase plays an essential role in endothelin‐1‐induced homotypic adhesion of human neutrophil granulocytes

  2002cites this paper
• Carrageenan-Induced Paw Reaction and Delayed-Type Hypersensitivity , and Proliferation , Cytokine Production ,3 , Inhibits T Lymphocyte n-Oxa 21 : 3 β Acid , A Novel Long Chain Polyunsaturated Fatty

  2001cites this paper
• Peroxynitrite induces integrin‐dependent adhesion of human neutrophils to endothelial cells via activation of the Raf‐1/MEK/Erk pathway

  2001cites this paper
• Docosahexaenoic acid modulates phorbol ester-induced activation of extracellular signal-regulated kinases 1 and 2 in NIH/3T3 cells

  2001cites this paper
• Arachidonic acid directly activates members of the mitogen-activated protein kinase superfamily in rabbit proximal tubule cells.

  2001cites this paper
• Activation of the Phosphatidylinositol 3-Kinase-Akt/Protein Kinase B Signaling Pathway in Arachidonic Acid-stimulated Human Myeloid and Endothelial Cells

  2001cites this paper
• Protein Kinases C Translocation Responses to Low Concentrations of Arachidonic Acid*

  2001cites this paper
• Signal transduction pathways for activation of extracellular signal‐regulated kinase by arachidonic acid in rat neutrophils

  2001cites this paper
• Arachidonic acid protects neonatal rat cardiac myocytes from ischaemic injury through epsilon protein kinase C.

  2001cites this paper
• Eicosapentaenoic acid and docosahexaenoic acid modulate MAP kinase (ERK1/ERK2) signaling in human T cells.

  2001cites this paper
• Arachidonic acid protects neonatal rat cardiac myocytes from ischaemic injury through ϵ protein kinase C

  2001cites this paper
• A Novel Long Chain Polyunsaturated Fatty Acid, β-Oxa 21:3n-3, Inhibits T Lymphocyte Proliferation, Cytokine Production, Delayed-Type Hypersensitivity, and Carrageenan-Induced Paw Reaction and Selectively Targets Intracellular Signals1

  2001cites this paper
• Arachidonic Acid Activates Mitogen-activated Protein (MAP) Kinase-activated Protein Kinase 2 and Mediates Adhesion of a Human Breast Carcinoma Cell Line to Collagen Type IV through a p38 MAP Kinase-dependent Pathway*

  2000cites this paper
• Mammary cancer promotion and MAPK activation associated with consumption of a corn oil-based high-fat diet.

  1999cites this paper
• Transient Ca2+‐dependent activation of ERK1 and ERK2 in cytotoxic responses induced by maitotoxin in breast cancer cells

  1999cites this paper
• Comparative study of the effects of polyunsaturated fatty acids and their metabolites on cell growth and tyrosine kinase activity in oesophageal carcinoma cells.

  1999cites this paper
• An essential role for mitogen‐activated protein kinases, ERKs, in preventing heat‐induced cell death

  1999cites this paper
• Role of prostaglandin H synthase isoforms in murine ear edema induced by phorbol ester application on skin.

  1999cites this paper
• Mitogen‐activated protein kinase and phosphorylation of connexin43 are not sufficient for the disruption of gap junctional communication by platelet‐derived growth factor and tetradecanoylphorbol acetate

  1999cites this paper
• Arachidonic acid induces the activation of the stress‐activated protein kinase, membrane ruffling and H2O2 production via a small GTPase Rac1

  1999cites this paper
• Nonsteroidal anti‐inflammatory drug metabolism potentiates interferon alfa signaling by increasing STAT1 phosphorylation

  1999cites this paper
• PHA / PMA-Stimulated Jurkat Cells-raf-MEK-ERK Cascade in ras p 21 Regulation of Lymphotoxin Production

  1999cites this paper
• Regulation of lymphotoxin production by the p21ras-raf-MEK-ERK cascade in PHA/PMA-stimulated Jurkat cells.

  1999cites this paper
• Mechanisms of protein A superantigen-induced signal transduction for proliferation of mouse B cell.

  1999cites this paper
• Involvement of protein kinase C, p38 MAP kinase and ERK in arachidonic acid-stimulated superoxide production in human neutrophils.

  1999cites this paper
• Interleukin-1 stimulates Jun N-terminal/stress-activated protein kinase by an arachidonate-dependent mechanism in mesangial cells.

  1999cites this paper
• Role of the Extracellular Signal-Regulated Protein Kinase Cascade in Human Neutrophil Killing of Staphylococcus aureus andCandida albicans and in Migration

  1999cites this paper
• 3′,5′‐Cyclic Guanosine Monophosphate Activates Mitogen‐Activated Protein Kinase in Rat Pinealocytes

  1999cites this paper
• Direct evidence that ERK regulates the production/secretion of interleukin‐2 in PHA/PMA‐stimulated T lymphocytes

  1999cites this paper
• Glucose Deprivation-induced Cytotoxicity and Alterations in Mitogen-activated Protein Kinase Activation Are Mediated by Oxidative Stress in Multidrug-resistant Human Breast Carcinoma Cells*

  1998cites this paper
• Arachidonate-induced tyrosine phosphorylation of epidermal growth factor receptor and Shc-Grb2-Sos association.

  1998cites this paper
• Induction of Mitogen-activated Protein Kinase Phosphatase-1 by Arachidonic Acid in Vascular Smooth Muscle Cells*

  1998cites this paper
• Phospholipase A2-mediated activation of mitogen-activated protein kinase by angiotensin II.

  1998cites this paper
• Pro‐ and anti‐apoptotic effects of K+ in HeLa cells

  1998cites this paper
• In vivo and in vitro assessment of mitogen activated protein kinase involvement during quail secondary palate formation

  1998cites this paper
• Differential translocation of protein kinase C isozymes by phorbol esters, EGF, and ANG II in rat liver WB cells.

  1998cites this paper
• A Relationship between 5-Lipoxygenase-activating Protein and bcl-xL Expression in Murine Pro-B Lymphocytic FL5.12 Cells*

  1998cites this paper
• Stimulation of p38 Phosphorylation and Activity by Arachidonic Acid in HeLa Cells, HL60 Promyelocytic Leukemic Cells, and Human Neutrophils

  1998cites this paper
• Integrin-dependent homotypic adhesion of neutrophils. Arachidonic acid activates Raf-1/Mek/Erk via a 5-lipoxygenase- dependent pathway.

  1998cites this paper
• Arachidonic acid activates Jun N-terminal kinase in vascular smooth muscle cells

  1998cites this paper
• Activation of phospholipase A2 in human neutrophils by polyunsaturated fatty acids and its role in stimulation of superoxide production.

  1998cites this paper
• Analysis of the interaction between arachidonic acid and metabotropic glutamate receptor activation reveals that phospholipase C acts as a coincidence detector in the expression of long‐term potentiation in the rat dentate gyrus

  1998cites this paper
• Differential translocation of protein kinase C isozymes by phorbol esters, EGF, and ANG II in rat liver WB cells.

  1998cites this paper
• Platelet‐derived growth factor‐induced disruption of gap junctional communication and phosphorylation of connexin43 involves protein kinase C and mitogen‐activated protein kinase

  1998cites this paper
• Signaling in unicellular eukaryotes.

  1998cites this paper
• Glycogen Synthase Kinase 3β and Extracellular Signal-Regulated Kinase Inactivate Heat Shock Transcription Factor 1 by Facilitating the Disappearance of Transcriptionally Active Granules after Heat Shock

  1998cites this paper
• Activation of neutral sphingomyelinase in human neutrophils by polyunsaturated‘qc fatty acids

  1997cites this paper