Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacterial lipopolysaccharide (LPS) is a potent activator of antibacterial responses by macrophages. Following LPS stimulation, the tyrosine phosphorylation of several proteins is rapidly increased in macrophages, and this event appears to mediate some responses to LPS. We now report that two of these tyrosine phosphoproteins of 41 and 44 kDa are isoforms of mitogen-activated protein (MAP) kinase. Each of these proteins was reactive with anti-MAP kinase antibodies and comigrated with MAP kinase activity in fractions eluted from a MonoQ anion-exchange column. Following LPS stimulation, column fractions containing the tyrosine phosphorylated forms of p41 and p44 exhibited increased MAP kinase activity. Inhibition of LPS-induced tyrosine phosphorylation of these proteins was accompanied by inhibition of MAP kinase activity. Additionally, induction of p41/p44 tyrosine phosphorylation and MAP kinase activity by LPS appeared to be independent of activation of protein kinase C, even though phorbol esters also induced these responses. These results demonstrate that LPS induces the tyrosine phosphorylation and activation of at least two MAP kinase isozymes. Since MAP kinases appear to modulate cellular processes in response to extracellular signals, these kinases may be important targets for LPS action in macrophages.
 ...
PMID:Bacterial lipopolysaccharide induces tyrosine phosphorylation and activation of mitogen-activated protein kinases in macrophages. 132 21

In this study we have verified the existence of a cytosolic phospholipase A2 (cPLA2) in rat-liver macrophages. Stimulation of these cells with phorbol 12-myristate 13-acetate (PMA), zymosan and lipopolysaccharide (LPS), but not with the Ca(2+)-ionophore A23187, leads to phosphorylation of cPLA2 and activation of mitogen-activated protein (MAP) kinase, supporting the hypothesis that MAP kinase is involved in cPLA2 phosphorylation. We show furthermore, that the tyrosine kinase inhibitor genistein prevents the LPS- but not the PMA- or zymosan-induced phosphorylation of cPLA2 and activation of MAP kinase, indicating that tyrosine kinases participate in LPS- but not in PMA- and zymosan-induced cPLA2 phosphorylation and MAP kinase activation. Phosphorylation of cPLA2 does not strongly correlate with stimulation of the arachidonic acid (AA) cascade: (1) A23187, a potent stimulator of AA release, fails to induce cPLA2 phosphorylation; (2) withdrawal of extracellular Ca2+, which inhibits PMA-stimulated AA release (Dieter, Schulze-Specking and Decker (1988) Eur. J. Biochem. 177, 61-67), has no effect on PMA-induced phosphorylation of cPLA2; (3) LPS induces cPLA2 phosphorylation within minutes, whereas increased AA release upon treatment with LPS is detectable for the first time after 4 h; and (4) genistein, which prevents LPS-induced cPLA2 phosphorylation, does not inhibit AA release in response to LPS. From these data we suggest that a rise in intracellular Ca2+, but not phosphorylation of cPLA2, is essential for activation of the AA cascade in rat-liver macrophages.
 ...
PMID:Role of cytosolic phospholipase A2 in arachidonic acid release of rat-liver macrophages: regulation by Ca2+ and phosphorylation. 757 53

Mammalian cells respond to endotoxic lipopolysaccharide (LPS) by activation of protein kinase cascades that lead to new gene expression. A protein kinase, p38, that was tyrosine phosphorylated in response to LPS, was cloned. The p38 enzyme and the product of the Saccharomyces cerevisiae HOG1 gene, which are both members of the mitogen-activated protein (MAP) kinase family, have sequences at and adjacent to critical phosphorylation sites that distinguish these proteins from most other MAP kinase family members. Both HOG1 and p38 are tyrosine phosphorylated after extracellular changes in osmolarity. These findings link a signaling pathway in mammalian cells with a pathway in yeast that is responsive to physiological stress.
 ...
PMID:A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. 791 33

We recently reported that cyclic AMP (cAMP) specifically inhibits lipopolysaccharide (LPS)-induced interleukin 1 beta (IL-1 beta) transcription initiation in astrocytic cells but enhances the LPS induction of IL-1 beta in monocytic cells. The purpose of this study was to determine how cAMP differentially regulates LPS-induced IL-1 beta transcription in these two cell types. Two essential components of the mitogen-activated protein (MAP) kinase signal-transduction pathway, extracellular-signal-regulated kinase (ERK2; p41 mapk) and Raf-1, have been shown to be targets of LPS stimulation in other cell types, and therefore may be linked to the regulation of IL-1 beta transcription. In the human astrocytic cell line, U-373MG, LPS was found to strongly activate (and cAMP to inhibit) both ERK2 and Raf-1. In the human monocytic cell line, THP-1, LPS minimally activated ERK2 and did not activate Raf-1. These findings suggest that, in astrocytic cells, elevated intracellular cAMP levels may negatively regulate LPS activation of IL-1 beta via the MAP kinase signalling pathway. In contrast, this pathway is not significantly activated by LPS in monocytic cells, thus inhibition by elevated intracellular cAMP levels would not affect IL-1 beta transcription.
 ...
PMID:Differential induction of the mitogen-activated protein kinase pathway by bacterial lipopolysaccharide in cultured monocytes and astrocytes. 857 86

We designed a microplate-based assay method for mitogen-activated protein (MAP) kinase. Using anion-exchanger resin, MAP kinases from murine macrophages were partially purified in 96-well plates. The activities of these purified enzymes correlated well with those detected in heretofore used assays. The micro-trap phosphorylation assay has advantages over conventional methods (immunoprecipitation, Western blotting for the detection of mobility shift, or kinase detection assay in myelin basic protein (MBP)-containing gel), in terms of sensitivity, economy and rapid execution for hundreds of samples. Using micro-trap phosphorylation assay, it was demonstrated that MAP kinase activities in macrophages were persistently increased by lipopolysaccharide (LPS) stimulation, and this activation was inhibited by polymyxin B or tyrosine kinase inhibitors. This method is expected to give a wide range of application, such as determining effects of drug inhibitors or antisense oligonucleotides on MAP kinases, or measuring the various protein kinases after specificity controls were done.
 ...
PMID:Micro-trap phosphorylation assay of mitogen-activated protein (MAP) kinases to detect their activation by lipopolysaccharides. 860 13

The expression of cytokine-induced neutrophil chemoattractants (CINC-1 and CINC-2) mRNA was studied in rat peritoneal cells stimulated with insoluble IgG/ovalbumin immune complexes. A dose- and time-dependent induction was observed in adherent cells, which was more prominent than that induced by the lipid mediator platelet-activating factor (PAF), comparable to that observed in response to 10 micrograms endotoxin in the absence of lipopolysaccharide (LPS)-binding protein, but lower than that produced by 1 mM dibutyryl cyclic AMP, a compound which stabilized transiently expressed genes containing AU-rich sequences in the 3' untranslated region. Analysis of CINC-1 protein by specific enzyme-linked immunosorbent assay confirmed the presence of CINC-1 in the supernatants at concentrations of approximately 4 nM, 4 h after addition of 100 micrograms/ml immune complexes. CINC-2 beta protein was detectable at a lower concentration (approximately 0.3 nM) under the same conditions. Attempts to relate CINC-1 induction with the pathways for cytoplasmic signaling showed a dissociation of Ca2+ mobilization and protein kinase C activation as judged from the small effect of thapsigargin and the lack of effect of phorbol ester. In contrast, these agents produced a marked mobilization of arachidonate linked to the MAP kinase-dependent activation of cytosolic phospholipase A2. The possible dependence of CINC-1 induction on the autocrine generation of lipid mediators was ruled out by a set of experiments including the use of the PAF receptor antagonist BB823, and the analysis of the effect of free arachidonate and leukotriene B4 on CINC-1 induction. Surprisingly, the inhibitor of leukotriene synthesis MK-886 in the range of concentration 1-10 microM inhibited CINC-1 induction by a mechanism that appears to be independent of its effect on eicosanoid production. Interestingly, CINC-1 induction appeared to be related to protein tyrosine phosphorylation reactions on the basis of both the appearance of several tyrosine-phosphorylated protein bands in lysates from adherent peritoneal cells treated with immune complexes and the complete blockade of CINC-1 induction by treatment with 1 microM herbimycin A, an inhibitor of src protein tyrosine kinases.
 ...
PMID:The expression of cytokine-induced neutrophil chemoattractants (CINC-1 and CINC-2) in rat peritoneal macrophages is triggered by Fc gamma receptor activation: study of the signaling mechanism. 881 63

Soluble staphylococcal peptidoglycan (sPGN) is an inducer of cytokine secretion and may activate macrophages through the CD14 lipopolysaccharide (LPS) receptor. To elucidate sPGN-activated signal transduction pathways, stimulation of mitogen-activated protein (MAP) kinases by sPGN was studied in mouse RAW264.7 macrophages. sPGN strongly activated extracellular signal-regulated kinase (ERK) 1 and ERK2, moderately activated c-Jun NH2 terminal kinase (JNK), and weakly activated p38 MAP kinase, in contrast to LPS, which strongly activated all of these kinases, and phorbol 12,13-dibutyrate (PDB), which strongly activated ERK1 and ERK2 but did not activate p38 or JNK. sPGN- and LPS-induced activation of ERK1 and ERK2, unlike PDB-induced activation, was sensitive to inhibition by herbimycin A and insensitive to inhibition by increased intracellular cAMP. These results demonstrate differential activation of MAP kinases by sPGN, similar but not identical activation of signal transduction pathways by sPGN and LPS, and different mechanisms of MAP kinase activation by bacterial stimulants and phorbol esters.
 ...
PMID:Differential activation of extracellular signal-regulated kinase (ERK) 1, ERK2, p38, and c-Jun NH2-terminal kinase mitogen-activated protein kinases by bacterial peptidoglycan. 884 16

Two chromatographically distinct stress-activated protein kinase kinases (SAPKKs) have been identified in several mammalian cells, termed SAPKK2 and SAPKK3, which activate the MAP kinase family member RK/p38 but not JNK/SAPK in vitro. Here we demonstrate that SAPKK2 is identical or very closely related to the MAP kinase kinase family member MKK3. However, under our assay conditions, SAPKK3 was the major activator of RK/p38 detected in extracts prepared from stress- or interleukin-1-stimulated epithelial (KB) cells, from bacterial lipopolysaccharide and tumour necrosis factor alpha-stimulated THP1 monocytes or from rabbit skeletal muscle. The activated form of SAPKK3 was purified from muscle to near homogeneity, and tryptic peptide sequences were used to clone human and murine cDNAs encoding this enzyme. Human SAPKK3 comprised 334 amino acids and was 78% identical to MKK3. The murine and human SAPKK3 were 97% identical in their amino acid sequences. We also cloned a different murine cDNA that appears to encode a SAPKK3 protein truncated at the N-terminus. SAPKK3 is identical to the recently cloned MKK6.
 ...
PMID:Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and epithelial cells. 886 44

The Drosophila MAP kinase DJNK is a homolog of the mammalian c-Jun amino-terminal kinase (JNK). Mutations in the DJNK gene correspond to the complementation group basket. DJNK is phosphorylated and activated by the Drosophila MAP kinase kinase HEP. Substrates of DJNK include the transcription factor DJun. DJNK participates in multiple physiological processes. Exposure to endotoxic lipopolysaccharide initiates an insect immune response and leads to DJNK activation. In addition, embryos lacking DJNK are defective in dorsal closure, a process in which the lateral epithelial cells migrate over the embryo and join at the dorsal midline. These data demonstrate that the DJNK signal transduction pathway mediates an immune response and morphogenesis in vivo.
 ...
PMID:A JNK signal transduction pathway that mediates morphogenesis and an immune response in Drosophila. 894 15

The addition of platelet-activating factor (PAF) to human neutrophils increases phosphorylation on tyrosine residues and stimulates the activity of p42erk2 mitogen-activated protein kinase (MAP kinase). This action is rapid and transient. In contrast, p42erk2, p44erk1 and the p40hera MAP kinase isoforms are all not tyrosine phosphorylated or activated in human neutrophils stimulated with low concentrations of lipopolysaccharide (LPS) in combination with serum. In spite of this, the PAF-induced tyrosine phosphorylation and activation of the p42erk2 MAP kinase are greatly potentiated in cells pretreated with LPS. More interestingly, although low concentrations of LPS do not affect MAP kinase isoforms in these cells, they cause the phosphorylation of cytosolic phospholipase A2 (cPLA2), as evidenced by a decrease in the electrophoretic mobility of the enzyme. In addition, this stimulus-induced upward shift in the mobility of the enzyme is not inhibited by the tyrosine kinase inhibitor, genistein. Furthermore, LPS increases the release of arachidonic acid in control and PAF-stimulated human neutrophils. These observations clearly show that cPLA2 can be phosphorylated and activated by kinases other than the currently known MAP kinases. It is proposed that there are MAP kinase-dependent and -independent mechanisms for the phosphorylation of cPLA2.
 ...
PMID:Effect of lipopolysaccharide on mitogen-activated protein kinases and cytosolic phospholipase A2. 894 37


1 2 3 4 5 6 7 8 9 10 Next >>