Disease relevance of MAPK11

• IUF1 expressed in Escherichia coli was unable to bind to DNA, but binding was induced by incubation with MgATP, SAPK2, and a MIN6 cell extract, which resulted in the conversion of IUF1 to a slower migrating form [1].
• Bleb formation but not apoptosis was blocked by extremely low concentrations of the actin polymerization inhibitor cytochalasin D or by the SAPK2 inhibitor SB203580, indicating that the two processes are not in the same linear cascade [2].
• The Epstein-Barr virus latent membrane protein 1 induces interleukin-10 in Burkitt's lymphoma cells but not in Hodgkin's cells involving the p38/SAPK2 pathway [3].
• Our previous studies have demonstrated that the activation of p38 MAP kinase (stress-activated protein kinase-2) and NF-kappaB are both required for a full UV-induced HIV gene expression response [4].

High impact information on MAPK11

• Selective activation of the p38 MAP kinase (=SAPK2) pathway by MAP kinase kinase 6 induced mRNA stabilization [5].
• We conclude that the HSP27-dependent actin polymerization-generating activity of SAPK2 associated with a misassembly of the focal adhesions is responsible for induction of membrane blebbing by stressing agents [2].
• SAPK2/p38-dependent F-actin reorganization regulates early membrane blebbing during stress-induced apoptosis [2].
• Cis-platinum, which activated SAPK2 but induced little ERK activity, also induced membrane blebbing that was dependent on the expression of HSP27 [2].
• Our results suggest that cellular functions previously attributed to SAPK1 and/or SAPK2 may be mediated by SAPK3 [6].

Biological context of MAPK11

• Overexpression of SAPK2 also stimulated PDX1-dependent transcription of a -50 to -250 region of the human insulin gene promoter linked to a firefly luciferase reporter gene [7].
• Although p38-2 and p38 phosphorylate the same substrates, the site specificity of phosphorylation can differ as shown by two-dimensional phosphopeptide analysis of Sap-1a [8].
• In conclusion, p38-2 may be an important component of the stress response required for the homeostasis of a cell [8].
• In contrast, selenite-induced apoptotic DNA fragmentation was observed in the absence of these changes, but was associated with the phosphorylation of c-Jun-NH2-terminal kinase 1/2 and p38 mitogen-activated protein kinase/stress-activated protein kinase 2 [9].
• Glucose-stimulated preproinsulin gene expression and nuclear trans-location of pancreatic duodenum homeobox-1 require activation of phosphatidylinositol 3-kinase but not p38 MAPK/SAPK2 [10].

Anatomical context of MAPK11

• Epidermal growth factor stimulation of trophoblast differentiation requires MAPK11/14 (p38 MAP kinase) activation [11].
• Here, we provide evidence that disruption of the microtubule structure rapidly triggers extracellular signal-regulated kinase (ERK) activation, whereas it was without effect on SAPK2 activity, which is commonly acknowledged to control pro-inflammatory cytokine production [12].
• Moreover, a recombinant E-selectin/Fc chimera quickly increased the activation of SAPK2/p38 in HT-29 cells [13].
• In turn, this triggers the activation of the SAPK2/p38 MAP kinase module, and promotes stress fiber formation and endothelial cell migration [14].
• Similarly, HeLa cells stably expressing a kinase-inactive mutant of SAPK2/p38 showed a decreased capacity to cross a layer of HUVEC [13].

Associations of MAPK11 with chemical compounds

• Unlike SAPK2, SAPK3 was not inhibited by the drug SB 203580 [6].
• Our results indicate that high glucose (a cellular stress) activates SAPK2 by a novel mechanism in which a wortmannin/LY 294002-sensitive component plays an essential role [1].
• Inhibiting protein degradation with MG132 caused the constitutive activation of SAPK2/p38, which was blocked by a pretreatment with either cycloheximide or heat shock [15].
• We conclude that egr-1 induction by anisomycin is mediated by p38/SAPK2 and probably by MSK1 [16].
• The effects of insulin were inhibited by the PtdIns 3-kinase inhibitors wortmannin and LY294002 and by the SAPK2 inhibitor SB203580, suggesting that its effects were mediated via activation of PtdIns 3-kinase and SAPK2 [17].

Regulatory relationships of MAPK11

• SAPK2 then activates IUF1 indirectly by activating a novel IUF1-activating enzyme [1].

Other interactions of MAPK11

• Consistent with this finding, high glucose activated mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP kinase-2) (a downstream target of SAPK2) in MIN6 cells, an effect that was also blocked by SB 203580 [1].
• Promyelocytic leukemia is a direct inhibitor of SAPK2/p38 mitogen-activated protein kinase [18].
• In contrast, SAPKK-2 activated SAP kinase-2, but not SAP kinase-1 in vitro [19].
• SAPKK-4 and SAPKK-5 were also eluted from Mono S at higher NaC1 concentrations than SAPKK-3 and these enzymes activated SAP kinase-1 but not SAP kinase-2 [19].
• Both kinases are inhibited by a class of pyridinyl imidazoles. p38-2 phosphorylation of ATF2 and Sap-1a but not Elk1 results in increased transcriptional activity of these factors [8].

Analytical, diagnostic and therapeutic context of MAPK11

• We report the molecular cloning of a novel isoform of p38 MAP kinase, p38 beta 2 [20].
• For six selected genes, p38/SAPK2-regulated expression was confirmed and further analysed by Northern blot experiments, demonstrating a complex regulation of these genes under stress conditions [21].

References