Disease relevance of Mapk9

• Further studies have highlighted the contributions of JNK1 and/or JNK2 to a range of biological and pathological processes [1].
• Disruption of JNK2 Decreases the Cytokine Response to Plasmodium falciparum Glycosylphosphatidylinositol In Vitro and Confers Protection in a Cerebral Malaria Model [2].
• Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance [3].
• Studies of nonobese diabetic mice demonstrated that disruption of the Mapk9 gene (which encodes the JNK2 protein kinase) decreased destructive insulitis and reduced disease progression to diabetes [4].
• This role of JNK2 to control the Th1/Th2 balance of the immune response represents a mechanism of protection against autoimmune diabetes [4].

High impact information on Mapk9

• Our data identify TIF-IA as a downstream target of the JNK pathway and suggest a critical role of JNK2 to protect rRNA synthesis against the harmful consequences of cellular stress [5].
• Substitution of Thr 200 by valine as well as knock-out of Jnk2 prevent inactivation and translocation of TIF-IA, leading to stress-resistance of Pol I transcription [5].
• The addition of exogenous IFNgamma during differentiation restores IL-12-mediated Th1 polarization in the JNK2-deficient mice [6].
• Further, the differentiation of precursor CD4+ T cells into effector Th1 but not Th2 cells is impaired in JNK2-deficient mice [6].
• JNK2 is preferentially bound to c-Jun in unstimulated cells, thereby contributing to c-Jun degradation [7].

Chemical compound and disease context of Mapk9

• To address the role of the JNK2 isoform in metabolic homeostasis, we intercrossed Jnk1(-/-) and Jnk2(-/-) mice and examined body weight and glucose metabolism in the resulting mutant allele combinations [3].

Biological context of Mapk9

• TNF-alpha-induced apoptosis was also suppressed in Jnk1 null fibroblasts but increased in Jnk2 null cells [8].
• In addition, JNK2 interfered with JNK1 activation via its "futile" phosphorylation by upstream kinases [8].
• JNK promoted the development of steatohepatitis as MCD diet-fed jnk1 null mice had significantly reduced levels of hepatic triglyceride accumulation, inflammation, lipid peroxidation, liver injury, and apoptosis compared with wild-type and jnk2 -/- mice [9].
• The patterns of gene expression in Jnk1(-/-), Jnk2(-/-), and wild-type cells are different [10].
• Impaired long-term potentiation in c-Jun N-terminal kinase 2-deficient mice [11].

Anatomical context of Mapk9

• Although JNK1 and JNK2 were shown to differentially regulate fibroblast proliferation, the underlying mechanistic basis remains unclear [7].
• Consequently, expression and activation of c-Jun, which depends on JNK activity, were impaired in Jnk1 null cells but enhanced in Jnk2 null cells [8].
• c-Jun NH(2)-terminal kinase (JNK)1 and JNK2 have distinct roles in CD8(+) T cell activation [12].
• Hepatocytes express both JNK1 and JNK2, but previous studies indicate that JNK1 is more important for hepatocyte proliferation [13].
• We therefore investigated the specific role of JNK2 in modulating long-term potentiation (LTP) in hippocampus during development, using JNK2-deficient mice [11].

Associations of Mapk9 with chemical compounds

• Tumor necrosis factor-induced toxic liver injury results from JNK2-dependent activation of caspase-8 and the mitochondrial death pathway [14].
• However, Safranin O-stained sections from the Jnk2(-/-) mice exhibited significantly less joint damage [15].
• JNK1 and JNK2 function was, therefore, investigated in the TNF-dependent, galactosamine/lipopolysaccharide (GalN/LPS) model of liver injury [14].
• JNK2 knockout mice and mice treated with JNK2 ASO exhibited partial protection against APAP [16].
• The morphological structure and the numbers of both NeuN, a specific neuronal marker, and GABA-positive neurons in the hippocampal areas were similar in wild-type and Jnk2(-/-) mice [11].

Regulatory relationships of Mapk9

• Macrophages lacking JNK2 displayed suppressed foam cell formation caused by defective uptake and degradation of modified lipoproteins and showed increased amounts of the modified lipoprotein-binding and -internalizing scavenger receptor A (SR-A), whose phosphorylation was markedly decreased [17].
• Our results suggest that, despite involvement in T(h)1/T(h)2 differentiation in vitro, Jnk2 is necessary neither for the induction nor effector phase of MOG35-55-induced EAE and nor is it required for antigen-specific IFN-gamma production [18].
• Additionally, phosphorylation levels of mitogen-activated protein kinase/extracellular-regulated kinase (ERK)-1/-2 and Jun kinase (JNK)-1/-2 were increased following prophylactic, but not acute, melatonin treatment [19].
• Role of Akt and c-Jun N-terminal kinase 2 in apoptosis induced by interleukin-4 deprivation [20].

Other interactions of Mapk9

• Neural differentiation was observed in wild-type, JNK2(-/-), and JNK3(-/-) cultures but not in JNK1(-/-) EBs [21].
• These results provide direct evidence that pfGPI induces TNF-alpha secretion through activation of MAPK pathways, including JNK2 [2].
• Liver injury and caspase activation were similarly decreased in jnk2 null mice after GalN/TNF treatment [14].
• The reduction of COX-2 expression was associated with greatly reduced viability of dominant-negative JNK-2-expressing cells during hypertonicity treatment [22].
• Thus, JNK2-dependent phosphorylation of SR-A promotes uptake of lipids in macrophages, thereby regulating foam cell formation, a critical step in atherogenesis [17].

Analytical, diagnostic and therapeutic context of Mapk9

• Fibroblast-like synoviocytes (FLS) were prepared from Jnk2(-/-) and wild-type mice, and JNK protein expression was determined by Western blot analysis [15].
• METHODS: Passive collagen-induced arthritis (CIA) was induced in Jnk2(-/-) and wild-type mice by administering anti-type II collagen antibodies [15].
• In the present work, primary embryo cells were isolated from wild-type, Jnk1(-/-) and Jnk2(-/-) mice and used for cDNA microarray analysis [10].
• In the present study, we examined whether JNK2 and -3 (JNK members most associated with neuronal loss) deficiency can rescue neuronal loss caused by facial and sciatic nerve axotomy in the neonate in vivo [23].
• A rapid enzyme-linked immunosorbent assay for the enzyme activity measurement of three well-known mitogen-activated protein (MAP) kinases, JNK2, ERK2, and p38 is described [24].

References