Disease relevance of Mapk14

• These studies demonstrate that an extremely typical physiological stress (hypoxia) causes selective activation of specific p38 signaling elements; and they also identify a downstream target of these pathways [1].
• In contrast to our expectation, treatment with the NPC31169 resulted in worse renal function, more proteinuria, and more severe glomerulosclerosis and tubulointerstitial injury. p38 inhibition resulted in marked cell proliferation in RK rats, with more proliferating tubular cells, myofibroblasts, and macrophages [2].
• To test the hypothesis that p38 mediates renal disease progression, we administered a novel p38 alpha inhibitor, NPC31169, to rats with remnant kidneys (RKs) [2].
• Activation and cellular localization of the p38 and JNK MAPK pathways in rat crescentic glomerulonephritis [3].
• In progressive anti-GBM disease, p38 and JNK activation in podocytes, glomerular endothelial cells, infiltrating macrophages, T cells, and myofibroblasts suggests that both the p38 and JNK MAPK pathways are important in chronic inflammation and fibrosis [3].

Psychiatry related information on Mapk14

• Differential activation of c-Jun N-terminal protein kinase and p38 in rat hippocampus and cerebellum after electroconvulsive shock [4].
• The intra-CA1 infusion of SP600125, at a dose that in naïve animals significantly reduced the phosphorylation levels of c-Jun without affecting the activity of ERK1/2 or p38 MAPK, enhanced short-term memory (STM) but blocked long-term memory (LTM) formation and retrieval of an inhibitory avoidance learning task [5].
• CONCLUSION: p38 MAPK plays an important role in the pressor response induced by central administration of IL-1 beta or footshock and change of motor activity after footshock in conscious rats [6].

High impact information on Mapk14

• The effects of dominant-interfering or constitutively activated forms of various components of the JNK-p38 and ERK signaling pathways demonstrated that activation of JNK and p38 and concurrent inhibition of ERK are critical for induction of apoptosis in these cells [7].
• In contrast, cardiac-specific p38alpha knockout mice show a 92.3% increase in neonatal cardiomyocyte mitoses [8].
• Protection by DEJL peptide binding was observed in loops spanning beta7-beta8 and alphaD-alphaE in p38alpha and ERK2 [9].
• Here we show that the p38 MAP kinase pathway, a parallel signaling cascade activated by distinct upstream kinases, mediates the induction of metabotropic glutamate receptor-dependent long-term depression at CA3-CA1 synapses [10].
• Although the function of the p42/p44 mitogen-activated protein (MAP) kinase pathway in long-term potentiation at hippocampal CA3-CA1 synapses has been well described, relatively little is known about the importance of the p38 MAP kinase pathway in synaptic plasticity [10].

Chemical compound and disease context of Mapk14

• Two unrelated selective inhibitors of p38 (SB203580 and SC-68376) dose dependently suppressed the arachidonic acid-induced pulmonary artery pressor response, edema formation, and bronchoconstrictor response in both control lungs and lungs that underwent preceding endotoxin priming [11].
• Both agents significantly attenuated PE-induced hypertrophy and inhibited both mitochondrial dysfunction and p38 and ERK1/2 MAPK activation [12].
• In the present study we demonstrate that p38, a member of the mitogen-activated protein kinase (MAPK) family, is essential for ascorbate- and laminin-induced myelination in Schwann cell-dorsal root ganglion neuron cocultures [13].
• Role of ERK and p38 mitogen-activated protein kinase cascades in gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide [14].
• Mitogen-activated protein kinases (p38 and c-Jun NH2-terminal kinase) are differentially regulated during cardiac volume and pressure overload hypertrophy [15].

Biological context of Mapk14

• The sst(2(a)) receptor-mediated ATF-2 activation and inhibition of proliferation induced by basic fibroblast growth factor (bFGF) were dependent on prolonged phosphorylation of p38 [16].
• In contrast, both interfering with p38 activity by overexpression of the dominant negative (DN) MKK6 mutant and inhibition of the JNK pathway by overexpression of the DN SEK1 mutant resulted in suppression of mitochondrial cytochrome c release, abrogating TGF-beta1-induced apoptosis [17].
• Extracellular signal-regulated kinase and p38 subgroups of mitogen-activated protein kinases regulate inducible nitric oxide synthase and tumor necrosis factor-alpha gene expression in endotoxin-stimulated primary glial cultures [18].
• Death from PUFA resulted from oxidative stress and was blocked by inhibition of ERK1/2, but not p38 MAPK or activator protein-1 signaling [19].
• Thus, arachidonic acid inhibits the insulin stimulation of G6PD mRNA accumulation by stimulating the p38 MAPK pathway, thereby inhibiting insulin signal transduction [20].

Anatomical context of Mapk14

• The bacterial lipopolysaccharide (LPS) was able to activate extracellular signal-regulated kinase (ERK) and p38 kinase subgroups of MAP kinases in microglia and astrocytes [18].
• Selective activation of p38alpha and p38gamma by hypoxia. Role in regulation of cyclin D1 by hypoxia in PC12 cells [1].
• A role for the extracellular signal-regulated kinase and p38 mitogen-activated protein kinases in interleukin-1 beta-stimulated delayed signal tranducer and activator of transcription 3 activation, atrial natriuretic factor expression, and cardiac myocyte morphology [21].
• The inhibition of extracellular signal-regulated kinase by PD98059 reduced NO release from both gangliosides- and GT1b-treated microglia whereas inhibition of p38 by SB203580 increased it rather slightly [22].
• Incubating the hepatocytes with the p38 MAPK inhibitor, SB203580, blocked the arachidonic acid inhibition of G6PD mRNA accumulation [20].

Associations of Mapk14 with chemical compounds

• We also examined the effect of Tyrphostin A46 (potent inhibitor of EGF-R and EGF-R kinase-dependent proliferation) on the above parameters [23].
• Phosphorylation of serine 105 enhanced the transcriptional potency of GATA4, which was sensitive to U0126 (MEK1 inhibitor) but not SB202190 (p38 inhibitor) [24].
• Whereas SB203580 inhibited endotoxin-induced NF-kappaB activation, pyrrolidine dithiocarbamate did not affect p38 phosphorylation in endotoxin-stimulated cells [25].
• In this study, we found that endotoxin causes activation of mitogen-activated protein kinases (MAPKs) (extracellular signal-regulated protein kinase [ERK] 1 and 2, p38, and c-Jun NH2-terminal kinase [JNK]) and nuclear factor kappaB (NF-kappaB) and production of H(2)O(2) in culture-activated HSCs [25].
• Thus, angiotensin II, by a mechanism that requires the participation of p38 MAPK, differentially regulates the expression of NF-kappaB-dependent genes in response to interleukin-1beta stimulation by controlling the duration of activation of ERK and NF-kappaB [26].

Physical interactions of Mapk14

• Treatment with a p38 MAPK inhibitor, PD169316, or transfection with a dominant-negative p38 MAPK construct reversed the effect of CD or ceramide to stabilize COX-2 mRNA [27].
• In this study, IFN-gamma enhancement of TNF-alpha-induced NF-kappaB binding affinity as well as p38 MAP kinase activation was observed [28].
• The data seem to indicate that JNK and p38 MAPK activations are not necessarily coupled to DNA binding of AP-1, which can be either increased or inhibited when these kinases are activated [29].
• More importantly, p38 kinase formed a complex with p53 after the treatment of CAPE for 0.5 hr [30].
• Furthermore, our data clearly show that an accelerating AMPA receptor endocytosis by stimulating the formation of guanyl nucleotide dissociation inhibitor-Rab5 complex is a potential downstream processing of p38 MAPK activation to mediate DHPG-LTD [31].

Enzymatic interactions of Mapk14

• IL-1 beta and TNF-alpha rapidly increased phosphorylated p38 MAP kinase abundance and activity [32].
• On collagen plates, mechanical stress rapidly activated p38 MAPK that phosphorylated p53 in smooth muscle cells [33].

Regulatory relationships of Mapk14

• However, inhibition of the JNK pathway suppressed p38 but induced transient ERK activation [17].
• Vav overexpression resulted in the constitutive activation of JNK1 with little or no effect on p38 mitogen-activated protein kinase and ERK2 [34].
• Interestingly, endothelin-1 activated signaling converges via p38 mitogen-activated protein kinase-dependent mechanism on ETS binding site, whereas this element inhibits extracellular signal-regulated kinase activated transcription [35].
• The p38 mitogen-activated protein kinase inhibitors SB202190 and SB203580 blocked Stat activation by NE, the epidermal growth factor receptor inhibitor AG1478 caused a small inhibition, but the phosphoinositide 3 kinase inhibitor LY294002 potentiated both responses [36].
• Inhibition of p38 mitogen-activated protein kinase enhances adrenergic-stimulated arylalkylamine N-acetyltransferase activity in rat pinealocytes [37].

Other interactions of Mapk14

• Stimulation with bFGF alone had no effect on the activity of either p38 or Akt but markedly enhanced p38 phosphorylation mediated by sst(2(a)) receptors, suggesting that a complex interplay exists between the transduction cascades activated by these distinct receptor types [16].
• Mechanisms of endotoxin-induced NO, IL-6, and TNF-alpha production in activated rat hepatic stellate cells: role of p38 MAPK [25].
• p38, a mitogen-activated protein kinase, is a major intracellular signaling molecule involved in inflammation [2].
• Elevated levels of cyclooxygenase-2 in antigen-stimulated mast cells is associated with minimal activation of p38 mitogen-activated protein kinase [38].
• Endothelin-1-specific activation of B-type natriuretic peptide gene via p38 mitogen-activated protein kinase and nuclear ETS factors [35].

Analytical, diagnostic and therapeutic context of Mapk14

• Interestingly, Western blot demonstrated increased ERK1/2 phosphorylation in p38-treated rats [2].
• Our data support the role of ICAM-1 on astrocytes as an inflammatory mediator in the CNS and also uncover a novel signal transduction pathway through p38 MAPK upon ICAM-1 ligation [39].
• RESULTS: In terms of glomerular MAPK activation, Western blotting identified the presence of both p-p38 and p-JNK in normal glomeruli, localized by immunohistochemistry to podocytes and epithelial cells of Bowman's capsule [3].
• Although no p38 MAPK activation occurred after 10 min of reperfusion, 2 h of reperfusion caused significant activation of p38 MAPK in nonischemic zone light and heavy fractions [40].
• 2. In cerebral arteries, S1P increased extracellular signal-regulated kinase (ERK)1/2 phosphorylation (5.2+/-1.4-fold increase) but did not activate p38 mitogen-activated protein kinase (p38MAPK) as assessed by immunoblotting [41].

References