Disease relevance of Mapk3

• Gene 33/RALT is induced by hypoxia in cardiomyocytes, where it promotes cell death by suppressing phosphatidylinositol 3-kinase and extracellular signal-regulated kinase survival signaling [1].
• We have developed a gene expression-based imaging system that detects and quantifies MAPK activity in prostate cancer tumors implanted into severe combined immunodeficient mice [2].
• Targeting Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase in the Mutant (V600E) B-Raf Signaling Cascade Effectively Inhibits Melanoma Lung Metastases [3].
• Angiogenesis and signaling through the RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade have been reported to play important roles in the development of hepatocellular carcinomas (HCC) [4].
• Collectively, these data indicate that calcineurin hypertrophic signaling is interconnected with PKCalpha, theta, and JNK in the heart, while PKCepsilon, beta, lambda, p38, and ERK1/2 are not involved in calcineurin-mediated hypertrophy [5].
• ERK1/2 signaling is not required for mediating physiologic or pathologic cardiac hypertrophy in vivo, although it does play a protective role in response to pathologic stimuli [6].

Psychiatry related information on Mapk3

• Although extracellular signal-regulated kinase (ERK) has been implicated in several neurobiological processes, including neuronal plasticity, its role in drug addiction remains poorly understood [7].
• Recent investigations have shown that three major striatal-signaling pathways (protein kinase A/DARPP-32, Akt/glycogen synthase kinase 3, and ERK) are involved in the regulation of locomotor activity by the monoaminergic neurotransmitter dopamine [8].

High impact information on Mapk3

• Early tyrosine phosphorylation, MAPK and AP-1 activation, and Ca2+ signaling were normal in mutant lymphocytes, but antigen receptor-induced NF-kappaB activation was absent [9].
• Activation of the Ras/MAPK signaling cascade is essential for growth factor-induced cell proliferation and differentiation [10].
• FRS2 functions as a lipid-anchored docking protein that targets signaling molecules to the plasma membrane in response to FGF stimulation to link receptor activation with the MAPK and other signaling pathways essential for cell growth and differentiation [10].
• A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway [10].
• PDE5A inhibition deactivates multiple hypertrophy signaling pathways triggered by pressure load (the calcineurin/NFAT, phosphoinositide-3 kinase (PI3K)/Akt, and ERK1/2 signaling pathways) [11].

Chemical compound and disease context of Mapk3

• Yersinia enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2, p38, and c-Jun NH2-terminal kinase. Correlation with its inhibitory effect on tumor necrosis factor-alpha production [12].
• AIMS/HYPOTHESIS: We investigated the effect of SB 203580, a pharmacological inhibitor of p38 mitogen-activated protein kinase (MAPK), on cardiac inflammation, cardiac fibrosis, and left ventricular function using an animal model of diabetic cardiomyopathy [13].
• Activation of both erk1/2 and p38MAPK occurs concomitant with prostatic epithelial cell proliferation and the initiation of prostate cancer while inactivation is contemporaneous with the emergence of the poorly differentiated metastatic and androgen-independent phenotype [14].
• Signal pathways which promote invasion and metastasis: critical and distinct contributions of extracellular signal-regulated kinase and Ral-specific guanine exchange factor pathways [15].
• The sesamin or sesamolin reduced caspase-3 and MAPK activation correlated well with diminished LDH release in BV-2 cells under hypoxia [16].

Biological context of Mapk3

• MAPK activation and phosphorylation of transcription factors are largely unaffected by H89, whereas induction of IE genes is inhibited and its characteristics markedly altered [17].
• Because Sox9 is essential for chondrocyte differentiation, we propose that FGFs and the MAPK pathway play an important role in chondrogenesis [18].
• Confluence of vascular endothelial cells induces cell cycle exit by inhibiting p42/p44 mitogen-activated protein kinase activity [19].
• These results, together with the fact that vanadate-sensitive phosphatase activity was higher in confluent cells, suggest that phosphatases play a role in the down-regulation of p42/p44 MAPK activity [19].
• Transactivation of Fra-1 and consequent activation of AP-1 occur extracellular signal-regulated kinase dependently [20].

Anatomical context of Mapk3

• However, in p44 MAPK-/- mice, thymocyte maturation beyond the CD4+CD8+ stage was reduced by half, with a similar diminution in the thymocyte subpopulation expressing high levels of T cell receptor (CD3high) [21].
• The specific role of the p44 MAPK isoform in the whole animal was evaluated by generation of p44 MAPK-deficient mice by homologous recombination in embryonic stem cells [21].
• We have previously reported that these morphogenic effects are dependent on MAPK activation at focal adhesions [22].
• Different protein tyrosine kinases are required for B cell antigen receptor-mediated activation of extracellular signal-regulated kinase, c-Jun NH2-terminal kinase 1, and p38 mitogen-activated protein kinase [23].
• We found that CpG-DNA induced extracellular signal-regulated kinase (ERK) activity in macrophages in a classic MEK-dependent way [24].

Associations of Mapk3 with chemical compounds

• In p44 MAPK-/- thymocytes, proliferation in response to activation with a monoclonal antibody to the T cell receptor in the presence of phorbol myristate acetate was severely reduced even though activation of p42 MAPK was more sustained in these cells [21].
• SHIP1 also significantly inhibits LPS-induced mitogen-activated protein kinase (MAPK) activation in TLR4-reconstitited COS7 cells [25].
• A putative DEF (docking for ERK FXFP) domain located in the proline-rich region of CdGAP is required for efficient binding and phosphorylation by ERK1/2 [26].
• Previously, we have demonstrated that deoxycholic acid (DCA)-induced signaling of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in primary hepatocytes is a protective response [27].
• Sodium orthovanadate, but not okadaic acid, restored p42/p44 MAPK activity in confluent cells [19].

Physical interactions of Mapk3

• The induction of AP-1 DNA binding activity by PG was also inhibited by these MAPK inhibitors [28].
• Erythropoietin receptor Y479 couples to ERK1/2 activation via recruitment of phospholipase Cgamma [29].
• Blocking ERK1/2 activation with the upstream inhibitor U0126 (10 microm) enhanced H(2)O(2)-induced (100-300 microm range) neurotoxicity and inhibited H(2)O(2)-mediated phosphorylation of the cyclic AMP regulatory binding protein (CREB), suggesting that ERK1/2 signals to survival under these conditions [30].
• This study investigated the participation of MAPK in the resumption of meiosis [germinal vesicle breakdown (GVB)] in oocytes and cumulus expansion using oocyte-cumulus cell complexes (OCC) from Mos-null mice (Mos(tm1Ev)/Mos(tm1Ev), hereafter Mos(-/-)) [31].
• 6. These findings provide new evidence for a complex network of interacting pathways involving CDK/MAPK that control apoptosis downstream of KA receptor activation in excitotoxic neuronal cell death [32].

Enzymatic interactions of Mapk3

• We show here that withdrawal of all survival factors from MK-PT cells is associated with a progressive increase in the activity of extracellular signal-regulated kinase-1 and -2 (ERK1/2) and a progressive decrease in phosphorylated Akt, a kinase critical to cell survival [33].
• This negative regulatory loop is further enhanced by the capacity of p42/p44 MAPK to phosphorylate MKP1 and 2 [34].
• Extracellular signal-regulated kinase 1 interacts with and phosphorylates CdGAP at an important regulatory site [26].
• Recombinant MEK2 produced in bacteria phosphorylates a kinase-inactive Erk-1 on tyrosine and threonine, whereas a kinase-inactive mutant MEK2 does not [35].
• Our studies showed an altered LDLr expression and altered phosphorylated MAPK in the liver of C57BL/6 mice during aging [36].

Co-localisations of Mapk3

• Immunofluorescent antibody staining of the MBs that formed showed that MAPK p38 was colocalized with ubiquitin and p62 in the MBs [37].

Regulatory relationships of Mapk3

• The results thus demonstrate a necessary role for PKC and p42 MAPK activation in 12-O-tetradecanoylphorbol-13-acetate induced mitogenesis and provide evidence for multiple PKC controls acting on this MAPK cascade [38].
• MEK is a dual-specificity kinase that activates the extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase upon agonist binding to receptors [39].
• MAPK mediation of hypertonicity-stimulated cyclooxygenase-2 expression in renal medullary collecting duct cells [40].
• Nuclear factor-inducing kinase plays a crucial role in osteopontin-induced MAPK/IkappaBalpha kinase-dependent nuclear factor kappaB-mediated promatrix metalloproteinase-9 activation [41].
• Moreover, the Epo-induced activation of ERK1 and ERK2 was augmented and prolonged in cells inducibly overexpressing CrkL [42].

Other interactions of Mapk3

• Survival function of ERK1/2 as IL-3-activated, staurosporine-resistant Bcl2 kinases [43].
• DCA caused activation of the ERK1/2 and JNK1/2 pathways [27].
• However, the mechanism of TNF-alpha mediated activation of extracellular signal-regulated kinase (ERK)/M1AP kinase has not been established clearly [44].
• We show here that in mouse embryos, Fibroblast growth factor receptors (FGFRs) are required for transcription of Dusp6, which encodes MKP3, an extracellular signal-regulated kinase (ERK)-specific MKP [45].
• In addition, SNP-induced apoptosis was slightly blocked by the selective p38 kinase inhibitor (SB203580) but not by the MAP/ERK1 kinase inhibitor (PD098059) [46].

Analytical, diagnostic and therapeutic context of Mapk3

• Western blots of tumor extracts showed that the elevated imaging signal in CWR22 xenografts correlated with elevated levels of phosphorylated extracellular signal-regulated kinase 1/2 but not p38 or c-Jun NH(2)-terminal kinase [2].
• We measured MAPK activity in two well-characterized xenograft models, CWR22 and LAPC9 [2].
• We report that ligation of microglial CD40 triggers activation of p44/42 mitogen-activated protein kinase (MAPK) [47].
• IL-6 mRNA and protein were measured using real-time PCR and ELISA, and MAPK pathway activation was studied [48].
• In summary, post-ischemic JNK and p38 (but not ERK1/2) activation was markedly reduced in a model of kidney ischemic preconditioning that was established in the mouse [49].

References