Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IL-9 is a Th2 cytokine that exerts pleiotropic activities on T cells, B cells, mast cells, hematopoietic progenitors, and lung epithelial cells, but no effect of this cytokine has been reported so far on mononuclear phagocytes. Human blood monocytes preincubated with IL-9 for 24 h before LPS or PMA stimulation exhibited a decreased oxidative burst, even in the presence of IFN-gamma. The inhibitory effect of IL-9 was specifically abolished by anti-hIL-9R mAb, and the presence of IL-9 receptors was demonstrated on human blood monocytes by FACS. IL-9 also down-regulated TNF-alpha and IL-10 release by LPS-stimulated monocytes. In addition, IL-9 strongly up-regulated the production of TGF-beta1 by LPS-stimulated monocytes. The suppressive effect of IL-9 on the respiratory burst and TNF-alpha production in LPS-stimulated monocytes was significantly inhibited by anti-TGF-beta1, but not by anti-IL-10Rbeta mAb. Furthermore, IL-9 inhibited LPS-induced activation of extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases in monocytes through a TGF-beta-mediated induction of protein phosphatase activity. In contrast, IL-4, which exerts a similar inhibitory effect on the oxidative burst and TNF-alpha release by monocytes, acts primarily through a down-regulation of LPS receptors. Thus, IL-9 deactivates LPS-stimulated blood mononuclear phagocytes, and the mechanism of inhibition involves the potentiation of TGF-beta1 production and extracellular signal-regulated kinase inhibition. These findings highlight a new target cell for IL-9 and may account for the beneficial activity of IL-9 in animal models of exaggerated inflammatory response.
 ...
PMID:IL-9 inhibits oxidative burst and TNF-alpha release in lipopolysaccharide-stimulated human monocytes through TGF-beta. 1193 70

Mammalian oocytes are arrested at metaphase of the second meiotic division (MII) before fertilization. When oocytes are stimulated by spermatozoa, they exit MII stage and complete meiosis. It has been suggested that an immediate increase in intracellular free calcium concentration and inactivation of maturation promoting factor (MPF) are required for oocyte activation. However, the underlying mechanism is still unclear. In the present study, we investigated the role of protein kinase C (PKC) and mitogen-activated protein (MAP) kinase, and their interplay in rat oocyte activation. We found that MAP kinase became dephosphorylated in correlation with pronucleus formation after fertilization. Protein kinase C activators, phorbol 12-myriatate 13-acetate (PMA) and 1,2-dioctanoyl-rac-glycerol (diC8), triggered dephosphorylation of MAP kinase and pronucleus formation in a dose-dependent and time-dependent manner. Dephosphorylation of MAP kinase was also correlated with pronucleus formation when oocytes were treated with PKC activators. Effects of PKC activators were abolished by the PKC inhibitors, calphostin C and staurosporine, as well as a protein phosphatase blocker, okadaic acid (OA). These results suggest that PKC activation may cause rat oocyte pronucleus formation via MAP kinase dephosphorylation, which is probably mediated by OA-sensitive protein phosphatases. We also provide evidence supporting the involvement of such a process in fertilization.
 ...
PMID:Activation of protein kinase C induces mitogen-activated protein kinase dephosphorylation and pronucleus formation in rat oocytes. 1208

Cardiac hypertrophy is induced by a variety of diseases, such as hypertension, valvular diseases, myocardial infarction, and endocrine disorders. Although cardiac hypertrophy may initially be a beneficial response that normalizes wall stress and maintains normal cardiac function, prolonged hypertrophy is a leading cause of heart failure and sudden death. A number of studies have elucidated molecules responsible for the development of cardiac hypertrophy, including the mitogen-activated protein (MAP) kinases pathway, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, and calcium/calmodulin-dependent protein phosphatase calcineurin pathway. These molecules may be targets for therapies designed to prevent the progression of cardiac hypertrophy. Numerous studies have focused on characterization of the intracellular signal transduction molecules that promote cardiac hypertrophy in order to clarify the molecular mechanisms, but there have been only a few reports on the inhibitory regulators of hypertrophic response. Recently, several molecules have attracted much attention as endogenous inhibitory regulators of cardiac hypertrophy. Enhancement of these inhibitory regulators would also seem to be a potential approach for the pharmacological treatment of hypertrophy. In this review, we summarize the inhibitory molecules of cardiac hypertrophy.
 ...
PMID:Inhibitory molecules in signal transduction pathways of cardiac hypertrophy. 1235 32

Cytosolic phospholipase A(2)-alpha (cPLA(2)-alpha) is a calcium-sensitive enzyme involved in receptor-mediated eicosanoid production. In resting cells, cPLA(2)-alpha is present in the cytosol and nucleus and translocates to membranes via its calcium-dependent lipid-binding (CaLB) domain following stimulation. cPLA(2)-alpha is also regulated by phosphorylation on several residues, which results in enhanced arachidonic acid release. Little is known about the factors controlling the nuclear localisation of cPLA(2)-alpha. Here the nuclear localisation of cPLA(2)-alpha in the EA.hy.926 human endothelial cell line was investigated. Nuclear localisation was dependent on proliferation, with subconfluent cells containing higher levels of nuclear cPLA(2)-alpha than contact-inhibited confluent or serum-starved cells. The broad-range protein kinase inhibitor staurosporine caused a decrease in the nuclear level of cPLA(2)-alpha, whereas the protein phosphatase inhibitor okadaic acid increased the level of nuclear cPLA(2)-alpha. Using inhibitors for specific mitogen-activated protein (MAP) kinases, both p42/44(MAPK) and p38(MAPK) were shown to be important in modulating nuclear localisation. Finally, inhibition of nuclear import and export using Agaricus bisporus lectin and leptomycin B, respectively, demonstrated that cPLA(2)-alpha contains functional nuclear localisation and export signals. Thus we have identified a novel mode of regulation of cPLA(2)-alpha. This, together with the increasing body of evidence supporting the role of nuclear lipid second messengers in gene expression and proliferation, may have important implications for controlling the growth of endothelial cells in angiogenesis and tumour progression.
 ...
PMID:Nuclear localisation of cytosolic phospholipase A2-alpha in the EA.hy.926 human endothelial cell line is proliferation dependent and modulated by phosphorylation. 1241 98

The Wis1-Sty1 mitogen-activated protein (MAP) kinase cascade is one of the major signaling systems involved in a wide range of stress responses in Schizosaccharomyces pombe. It is known that Deltawis1 and Deltasty1 mutants exhibit highly pleiotropic phenotypes, including a phenotype of temperature sensitivity for growth. In this study, we screened multicopy suppressor genes that allow both the Deltawis1 and Deltasty1 mutants to grow simultaneously at a non-permissive temperature, 37 degrees C. Two such multicopy suppressors were cloned and characterized as sds23(+) and hxk2(+) genes. The former is known to specify a protein that functions as a multicopy suppressor for mutations of the PP1 protein phosphatase and the 20S cyclosome/anaphase-promoting complex (APC), and the latter encodes hexokinase 2. It was revealed that the multicopy sds231 gene restored a defect in the mating efficiency caused by the Deltawis1 and Deltasty1 mutations, whereas the multicopy hxk2(+) gene suppressed a phenotype of heat-shock sensitivity for growth of these mutant cells. These findings are discussed with special reference to the Wis1-Sty1 MAP kinase signaling pathway in S. pombe.
 ...
PMID:Characterization of multicopy suppressor genes that complement a defect in the Wis1-Sty1 MAP kinase cascade involved in stress responses in Schizosaccharomyces pombe. 1250 21

We report isolation of two novel rice (Oryza sativa L.) mitogen-activated protein kinases (MAPKs), OsMSRMK3 (multiple stress responsive) and OsWJUMK1 (wound- and JA-uninducible) that most likely exist as single copy genes in its genome. OsMSRMK3 and OsWJUMK1 encode 369 and 569 amino acid polypeptides having the MAPK family signature and phosphorylation activation motifs TEY and TDY, respectively. Steady state mRNA analyses of these MAPKs with constitutive expression in leaves of two-week-old seedlings revealed that OsMSRMK3 was up-regulated upon wounding (by cut), jasmonic acid (JA), salicylic acid (SA), ethylene, abscisic acid, hydrogen peroxide (H(2)O(2)), protein phosphatase inhibitors, chitosan, high salt/sugar, and heavy metals, whereas OsWJUMK1 not induced by either wounding, JA or SA, showed up-regulation only by H(2)O(2), heavy metals, and cold stress (12 degrees C). Moreover, these MAPKs were developmentally regulated. These results strongly suggest a role for OsMSRMK3 and OsWJUMK1 in both stress-signalling pathways and development in rice.
 ...
PMID:Novel rice MAP kinases OsMSRMK3 and OsWJUMK1 involved in encountering diverse environmental stresses and developmental regulation. 1250 18

OBJECTIVE: To elucidate the molecular mechanisms involved in hypoxic preconditioning (HPC) of neonatal rat cardiomyocytes against hypoxia/reoxygenation (H/R) injury. METHODS: Cardiomyocytes from neonatal Sprague-Dawley rats were randomly distributed into the following experimental groups: (1) HPC group: 20 min of hypoxia was performed to induce hypoxic preconditioning. Twenty four hours after HPC, cardiomyocytes were exposed to lethal hypoxia for 3 h followed by 3 h normoxia (reoxygenation). (2) Hypoxia/reoxygenation (H/R) group: cardiomyocytes were directly subjected to hypoxia (3 h) followed by reoxygenation (3 h). (3) PD98059+HPC (PD+HPC) group: cardiomyocytes were preincubated with PD98059 (a selective MEK-1/2 inhibitor, 50 mumol/l) 10 min prior to HPC. (4) BDM+HPC group: cardiomyocytes were pretreated with an activator of protein phosphatase 2,3-butanedione monoxide (BDM, 20 mmol/l) 10 min prior to HPC. (5) Control group: cardiomyocytes were incubated in cell incubator for 30 h. Viability of cardiomyocytes was assessed by MTT assay. Lactate dehydrogenase (LDH) activity in medium was determined using a LDH assay kit. Activity of p42/44 mitogen-activated protein kinases (p42/44 MAPKs) was detected using Western blotting method. SDS-PAGE mobility shift experiments were performed to determine phosphorylation of Hypoxia-inducible factor-1alpha (HIF-1alpha). RESULTS: HPC promoted survival and membrane integrity of cardiomyocytes subjected to subsequent sustained H/R. The protective effects of HPC were completely abolished either by PD98059 [a selective inhibitor of MEK-1/2 (upstream activators of p42/44 MAPKs)], or by BDM (an activator of protein phosphatase). Western blot analysis showed activated p42/44 MAPKs in whole cell extracts from hypoxic preconditioned cardiomyocytes. SDS-PAGE mobility shift experiments showed increased phophorylation level of HIF-1alpha in HPC group, and the phosphorylation can be blocked by PD98059 or BDM. CONCLUSIONS: HPC protects neonatal cardiomyocytes against H/R injury by promoting cardiomyocyte survival and membrane integrity. The protective mechanism might be attributed to upregulation of HIF-1alpha phosphorylation which may be induced by P42/44 MAPKs.
 ...
PMID:Hypoxic preconditioning of cardiomyocytes and cardioprotection: phophorylation of HIF-1alpha induced by p42/p44 mitogen-activated protein kinases is involved. 1456 22

Our previous studies showed that bacterial heat shock protein 60 (hsp60) induces cultured epithelial cell proliferation within 24 h. Here we investigated the long-term effects of heat shock protein 60 isolated from Actinobacillus actinomycetemcomitans on skin keratinocyte (HaCaT cell line) viability and the cell signaling involved. Prolonged incubation in the presence of hsp60 increased the rate of epithelial cell death. The number of viable cells in hsp60-treated culture was 37% higher than the number in the control at 24 h but 27% lower at 144 h. A kinetics study of the effect of hsp60 on the phosphorylation of mitogen-activated protein kinases (MAPKs) involving Western blotting with phospho-specific antibodies showed that in addition to a transient early increase in p38 levels, a second peak appeared in keratinocytes 24 h after the addition of hsp60. In contrast, prolonged incubation with hsp60 caused a decrease in the level of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) compared with that in the controls, possibly as a result of protein phosphatase activity. We found that hsp60 increased the levels of several phosphatases, including MAP-2, which strongly dephosphorylates ERK1/2. Moreover, hsp60 increased the level of tumor necrosis factor alpha (TNF-alpha) in culture medium in a dose-dependent manner. TNF-alpha added to culture showed a cytotoxic effect on epithelial cells, particularly with longer incubation periods. TNF-alpha also induced the phosphorylation of p38. Finally, our results show that bacterial hsp60 inhibited stress-induced synthesis of cellular hsp60. Therefore, several cell behavior changes caused by long-term exposure to bacterial hsp60 may lead to impaired epithelial cell viability.
 ...
PMID:Long-term effect of heat shock protein 60 from Actinobacillus actinomycetemcomitans on epithelial cell viability and mitogen-activated protein kinases. 1468 78

Glucagon-like peptide-1 (GLP-1), an incretin with glucose-dependent insulinotropic and insulin-independent antidiabetic properties, has insulin-like effects on glucose metabolism in extrapancreatic tissues participating in overall glucose homeostasis. These effects are exerted through specific receptors not associated with cAMP, an inositol phosphoglycan being a possible second messenger. In rat hepatocytes, activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB), protein kinase C (PKC) and protein phosphatase 1 (PP-1) has been shown to be involved in the GLP-1-induced stimulation of glycogen synthase. We have investigated the role of enzymes known or suggested to mediate the actions of insulin in the GLP-1-induced increase in glycogen synthase a activity in rat skeletal muscle strips. We first explored the effect of GLP-1, compared with that of insulin, on the activation of PI3K, PKB, p70s6 kinase (p70s6k) and p44/42 mitogen-activated protein kinases (MAPKs) and the action of specific inhibitors of these kinases on the insulin- and GLP-1-induced increment in glycogen synthase a activity. The study showed that GLP-1, like insulin, activated PI3K/PKB, p70s6k and p44/42. Wortmannin (a PI3K inhibitor) reduced the stimulatory action of insulin on glycogen synthase a activity and blocked that of GLP-1, rapamycin (a 70s6k inhibitor) did not affect the action of GLP-1 but abolished that of insulin, PD98059 (MAPK inhibitor) was ineffective on insulin but blocked the action of GLP-1, okadaic acid (a PP-2A inhibitor) and tumour necrosis factor-alpha (a PP-1 inhibitor) were both ineffective on GLP-1 but abolished the action of insulin, and Ro 31-8220 (an inhibitor of some PKC isoforms) reduced the effect of GLP-1 while completely preventing that of insulin. It was concluded that activation of PI3K/PKB and MAPKs is required for the GLP-1-induced increment in glycogen synthase a activity, while PKC, although apparently participating, does not seem to play an essential role; unlike in insulin signaling, p70s6k, PP-1 and PP-2A do not seem to be needed in the action of GLP-1 upon glycogen synthase a activity in rat muscle.
 ...
PMID:Cell signalling of glucagon-like peptide-1 action in rat skeletal muscle. 1501 93

Adenosine enhances nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. We found that adenosine increases NGF-induced phosphorylation of extracellular signal-regulated kinase (ERK), but decreases the duration of phosphorylation of p38 mitogen-activated protein (MAP) kinase. Therefore, we further examined the involvement of protein phosphatase in these effects of adenosine. FK506, a specific calcineurin inhibitor, inhibited the enhancing effect of adenosine on the NGF-induced neurite outgrowth and increased the duration of p38 MAP kinase phosphorylation without affecting ERK phosphorylation. These results suggest that adenosine decreases the duration of p38 MAP kinase via calcineurin activation, which contributes to the enhancement of NGF-induced neurite outgrowth.
 ...
PMID:Calcineurin contributes to the enhancing effect of adenosine on nerve growth factor-induced neurite outgrowth via the decreased duration of p38 mitogen-activated protein kinase phosphorylation. 1515 59


<< Previous 1 2 3 4 5 6 7 Next >>