Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulation of intercellular adhesion molecule-1 (ICAM-1) expression by renal tubular epithelial cells (TEC) has been studied in vitro. ICAM-1 expression in TEC is stimulated with phorbol 12-myristate 13-acetate (PMA), but not with forskolin, suggesting a role for protein kinase C (PKC) but not for protein kinase A (PKA). The tumor necrosis factor-alpha- (TNF-alpha) and interleukin-1 (IL-1)-stimulated ICAM-1 expression in TEC is blocked with the PKC/PKA inhibitor staurosporine, and also with the PKC-selective inhibitor calphostin C. The TNF-alpha-stimulated ICAM-1 expression is resistant however to downregulation of PKC with PMA. The TNF-alpha- and IL-1-stimulated ICAM-1 expression is also inhibited with the transcriptional inhibitor actinomycin D and with the protein synthesis inhibitor cycloheximide. Thus, ICAM-1 expression by TEC may involve a downregulation-resistant PKC which induces ICAM-1 expression at a transcriptional level.
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PMID:Tumor necrosis factor-alpha- and interleukin-1-stimulated intercellular adhesion molecule-1 expression by murine renal tubular epithelial cells is transcriptionally regulated and involves protein kinase C. 128 23

Lymphocyte adhesion to target cells is mediated, in part, by the interaction of lymphocyte function-associated Ag-1 (LFA-1) with intercellular adhesion molecule-1 (ICAM-1). Cells of the B cell line, JY, express both coreceptors and have been used as a model for intercellular adhesion mediated by these molecules. Elevation of the intracellular cAMP concentration ([cAMP]i), by any of several reagents, for periods as brief as 30 min, led to enhanced intercellular adhesion in a concentration dependent manner 5 to 8 h later. Two protein kinase A inhibitors, KT5720 and H-89, but not the protein kinase C inhibitor calphostin C, blocked the effects of elevated [cAMP]i. These data suggest a role for protein kinase A in this response. The adhesion augmented by increased [cAMP]i was due to LFA-1/ICAM-1 interactions between cells because it was blocked by either anti-LFA-1 or anti-ICAM-1 mAb. Elevated [cAMP]i induced cell surface patching of LFA-1, but not ICAM-1, and this redistribution preceded intercellular adhesion. Finally, redistribution of LFA-1 was not mediated by the cytoskeleton. These results suggest a model in which transient activation of protein kinase A results in increased local concentration of LFA-1 at the cell surface and in augmented long term adhesion mediated by this integrin.
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PMID:Lymphocyte adhesion mediated by lymphocyte function-associated antigen-1. I. Long term augmentation by transient increases in intracellular cAMP. 135 27

Ag independent adhesion between lymphocytes and target cells is mediated in part by the interaction between lymphocyte function associated Ag-1 (LFA-1) and its coreceptor intercellular adhesion molecule-1 (ICAM-1). Within minutes, PMA treatment of JY cells, which express both LFA-1 and ICAM-1, induced capping of LFA-1 and augmentation of intercellular adhesion lasting for several hours. However, over the course of 15 to 30 min, both of these events were blocked by elevation of intracellular cAMP concentration ([cAMP]i) presumably via activation of protein kinase A. This short term inhibition of protein kinase C-induced adhesion was in contrast to the long term augmentation of adhesion caused by increased [cAMP]i as demonstrated in the companion article. Intercellular adhesion, due to LFA-1/ICAM-1 interactions, could also be induced by LPS treatment of JY cells. At submaximal concentrations, the extent of aggregation induced by LPS had two maxima, one at 30 to 60 min and the other with a plateau at 5 to 8 h. LPS is known to activate protein kinase C and we show that LPS treatment induced increased [cAMP]i. Using inhibitors of protein kinases C and A, possible mediators of the two components of adhesion induced by LPS could be identified. The early component was abrogated by inhibition of protein kinase C although the later component was unaffected. In contrast, an inhibitor of protein kinase A had no affect on the early component and attenuated, but did not entirely eliminate, the late component. These results suggest a model of sequential induction, inhibition, and reinduction of LFA-1/ICAM-1-mediated lymphocyte adhesion that is regulated by temporally ordered actions and interactions of protein kinases C and A.
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PMID:Lymphocyte adhesion mediated by lymphocyte function-associated antigen-1. II. Interaction between phorbol ester- and cAMP-sensitive pathways. 135 28

Monocyte adherence to the endothelium, their penetration to the subendothelial space and excessive lipid accumulation (foam cell formation) are the initial events in atherogenesis. Scavenger receptors have been reported to play an important role in foam cell formation, since modified low density lipoproteins can be taken up via scavenger receptors in a non-down-regulated fashion. In this study we demonstrate that stimulation of scavenger receptors in endothelial cells induces the expression of endothelial adhesion molecules. Polyinosinic acid (poly I), a known scavenger receptor ligand, significantly induced the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin on human umbilical vein endothelial cells when compared with polycytidylic acid (poly C), a structurally related compound to poly I, which does not bind to the scavenger receptor. The effect of scavenger receptor ligands on the endothelial cell line EA hy. 926 was also tested. Poly I up-regulated ICAM-1 expression also on EA hy. 926 cells, while it had no effect on IL-1 beta or tumour necrosis factor-alpha (TNF-alpha) production on the same cell line. Poly I-induced ICAM-1 expression on EA hy. 926 cells could be inhibited by H7, a protein kinase C inhibitor, while HA 1004, a preferential protein kinase A inhibitor, had no effect on ICAM-1 expression. The role of protein kinase C in scavenger receptor-mediated adhesion molecule upregulation was confirmed by the ability of poly I to directly activate protein kinase C, when measured with 3H-phorbol dibutyrate binding to EA hy. 926 cells, while poly C again was ineffective.
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PMID:Regulation of endothelial adhesion molecules by ligands binding to the scavenger receptor. 768 91

It is well known that the exposure of endothelial cells to IL-1 beta induces an increase in endothelial cell adhesiveness for leucocytes. Using rat heart endothelial cells we found that exposure of endothelial cells to IL-1 beta (100 U/ml) induces a 133-fold increase in the intracellular concentration of cyclic-GMP; from 11.5 +/- 0.2 fM to 1530 +/- 117.8 fM (per 10(6) cells). Therefore, we examined whether cyclic-GMP is involved in the regulation of endothelial adhesiveness for leucocytes. Cyclic-GMP analogue, dibutyryl cyclic-GMP Methylene blue, an inhibitor of guanylate cyclaese, and KT5823, a specific inhibitor of cyclic-GMP-dependent protein kinase, inhibited both basal as well as IL-1 beta-induced endothelial cell adhesiveness for leucocytes, and KT5823 abolished the dibutyryl-cyclic-GMP-induced increase in endothelial adhesiveness. The effect of cyclic-GMP, induced by IL-1 beta treatment, on the endothelial adhesiveness may be either direct or indirect because of the time-gap between the rise in cyclic-GMP level and the increase of endothelial adhesiveness. IL-1 beta (100 U/ml) and dibutyryl-cyclic-GMP (0.01 mM) both induced an increase in the expression of intercellular adhesion molecule-1 by endothelial cells. However, the fact that KT5823 failed to prevent this increase, suggests that, although the IL-1 beta-induced increase in adhesiveness is caused by the increase in intracellular levels of cyclic-GMP, it may not be mediated through intercellular adhesion molecule-1. In conclusion, the results obtained indicate that endothelial cell adhesiveness for leucocytes is, in part, regulated by the cyclic-GMP-dependent signal transduction pathway.
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PMID:IL-1 beta-stimulated leucocyte-endothelial adhesion is regulated, in part, by the cyclic-GMP-dependent signal transduction pathway. 791 3

We examined the effect of agents which augment intracellular levels of cyclic adenosine monophosphate on the expression of adhesion molecules on human umbilical vein endothelial cells. Surface protein expression of vascular cell adhesion molecule-1, endothelial leukocyte adhesion molecule-1, or intercellular adhesion molecule-1, which is induced by tumor necrosis factor, interleukin-1, and lipopolysaccharide, was not induced by pentoxyfilline, a phosphodiesterase inhibitor, nor by dibutyryl cyclic adenosine monophosphate. Furthermore, neither of these two cyclic adenosine monophosphate elevating agents nor HA 1004, an inhibitor of the cyclic adenosine monophosphate-dependent protein kinase, had any effect on tumor necrosis factor-alpha-induced surface expression of these adhesion molecules. Likewise, cyclic adenosine monophosphate elevating agents were without effect on leukocyte adherence to endothelium stimulated either with these agents alone or in combination with tumor necrosis factor-alpha. Additionally, activators of the stimulatory or inhibitory guanine nucleotide-dependent binding proteins did not affect TNF-alpha-induced surface expression of endothelial leukocyte adhesion molecule-1 or vascular cell adhesion molecule-1.
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PMID:Cytokine-induced adhesion molecule expression on human umbilical vein endothelial cells is not regulated by cyclic adenosine monophosphate accumulation. 839 31

Several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1) are expressed by astrocytes, the predominant glial cell of the central nervous system (CNS). Such molecules are important in the trafficking of leukocytes to sites of inflammation, and in lymphocyte activation. ICAM-1 is constitutively expressed by neonatal rat astrocytes, and expression is enhanced by the proinflammatory cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma), with IL-1 beta and TNF-alpha being the strongest inducers. In this study, we have examined the nature of the second messengers involved in ICAM-1 gene expression induced by the cytokines IL-1 beta and TNF-alpha. Our results indicate that stimuli related to protein kinase C (PKC) such as the phorbol ester phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 increase ICAM-1 mRNA expression, whereas cyclic nucleotide analogs and PKA agonists have no effect. Pharmacologic inhibitors of PKC such as H7, H8, and calphostin C inhibit ICAM-1 gene expression inducible by IL-1 beta and TNF-alpha. Prolonged treatment of astrocytes with PMA results in a time-dependent downregulation of the PKC isoforms alpha, delta, and epsilon, and a concomitant diminution of ICAM-1 mRNA expression induced by IL-1 beta, TNF-alpha, and PMA itself at specific time points post-PMA treatment. These data, collectively, demonstrate a role for various PKC isoforms in IL-1 beta and TNF-alpha enhancement of ICAM-1 gene expression in rat astrocytes.
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PMID:Interleukin 1-beta- and tumor necrosis factor-alpha-mediated regulation of ICAM-1 gene expression in astrocytes requires protein kinase C activity. 853 Jan 84

We investigated the role of surface adhesion molecules in regulating vascular permeability, in vitro and in vivo. Cultured rat endothelial cells (RECs) express Thy-1, intercellular adhesion molecule-1 (ICAM-1), and CD44. Permeability of albumin across the REC monolayer increased through the interaction of Thy-1 and anti-Thy-1 monoclonal antibodies (mAbs), but no increase was seen through ICAM-1 and anti-ICAM-1, CD44 and anti-CD44, and RT1A and anti-RT1A mAbs. The potential of anti-Thy-1 mAb for permeability increase depended on antibody concentration, it peaked at 12h, and was neither mediated by injury nor by growth modulation to the REC monolayer. Effect of anti-Thy-1 mAb was inhibited significantly by the calmodulin antagonist W-7 or the protein kinase inhibitors H-7 and HA-1004, and was completely blocked by the combined addition of W-7 and H-7. It seems likely that both calmodulin and protein kinases are involved in related intracellular signal pathways. Thy-1 expression on RECs was up-regulated with IL-1 beta treatment and was down-regulated with mixed lymphocyte reaction (MLR) supernatant treatment. Although Thy-1 expression on rat vascular endothelium in vivo was not detected, the expression of Thy-1 was induced on dermal endothelial cells at the site of inflammation induced by Freund's complete adjuvant (FCA). Vascular permeability in the inflamed dermis significantly increased when anti-Thy-1 but not anti-ICAM-1, anti-CD44, or anti-RT1A mAbs were given intravenously. The collective evidence suggests that inducible Thy-1 on the endothelium is one important regulatory event in vascular permeability at sites of inflammation.
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PMID:[Expression and role of Thy-1 on endothelial cells at sites of inflammation--a novel function of Thy-1; vascular permeability regulation]. 854 76

Phorbol ester (TPA)-induced increase in cell surface expression of adhesion structures, i.e. intercellular adhesion molecule-1 (ICAM-1, CD54), beta 2 integrin LFA-1 (CD11a), complement-regulatory cell membrane protein-protein (CD59) and leukocyte common antigen (CD45) in human erythroid/myeloid leukemia cell line K-562 was inhibited by staurosporine, an inhibitor with broad, non-selective protein kinase inhibitory profile, but not by CGP 41,251, a benzoylated staurosporine derivative with the selective protein kinase C (PKC) inhibitory activity. Neither staurosporine nor CGP 41,251 modulated TPA-induced down-regulation of transferrin receptor (CD71). These data suggest that phorbol ester-induced cell surface antigen modulations in K-562 cells are predominantly mediated by PKC-independent signalling pathways.
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PMID:Phorbol ester (TPA)-induced differential modulation of cell surface antigens in human pluripotential leukemia (K-562) cell line: effects of protein kinase inhibitors with broad- and PKC selective inhibitory activity. 855 4

The aim of this study was to analyse the potential roles of protein kinase enzymes in tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) induced expression of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on human umbilical vein endothelial cells (HUVEC). The authors observed a marked increase in ICAM-1 and VCAM-1 expression on HUVEC stimulated for 24 h by TNF-alpha (10 ng/ml) or IL-1 (20 ng/ml). Pre-treatment of HUVEC for 30 min with protein tyrosine kinase (PTK) inhibitors genistein and herbimycin A (10 micrograms/ml and 0.5 microgram/ml, respectively) before stimulation with IL-1 did not affect the expression of these molecules. Similar results were observed with respect to VCAM-1 expression on HUVEC stimulated by TNF-alpha. In contrast, pre-incubation of HUVEC with PTK inhibitors prior to the addition of TNF-alpha significantly enhanced subsequent expression of ICAM-1, although spontaneous expression of ICAM-1 on unstimulated HUVEC was unaffected. Western blot analysis demonstrated a significant increase in phosphorylated tyrosine protein levels in HUVEC stimulated by TNF-alpha, and significantly lower levels of these proteins in TNF-alpha stimulated HUVEC pre-treated with PTK inhibitors. These results demonstrate that IL-1 induced ICAM-1 and VCAM-1 expression does not result from activation of PTK-dependent pathways. In the case of TNF-alpha induced responses, the selective co-stimulatory effect of this cytokine in combination with PTK inhibitors on ICAM-1 expression suggests a complicated intracellular pathway of TNF-alpha induced ICAM-1 expression, possibly involving down-modulation of increases in ICAM-1 by PTK enzymes.
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PMID:Role of tyrosine kinase enzymes in TNF-alpha and IL-1 induced expression of ICAM-1 and VCAM-1 on human umbilical vein endothelial cells. 910 26


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