Summary

Name MAPK11
Full Name Mitogen-activated protein kinase 11
Synonyms MAP kinase 11, MAPK 11, Mitogen-activated protein kinase p38 beta, MAP kinase p38 beta, p38b, Stress-activated protein kinase 2b, SAPK2b, p38-2 | PRKM11, SAPK2, SAPK2B
Primary ID Q15759
Links - -
Type protein
Relations 33
Inhibitors SB 203580; N-[4-[2-ethyl-4-(3-methylphenyl)-5-thiazolyl]-2-pyridinyl]benzamide; SB-202190; VX-745; regorafenib
Function Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK11 functions are mostly redundant with those of MAPK14. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment.

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates activity img/direct-activation.png phosphorylation PIAS2 0.267
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TCF3 0.412
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle
+ up-regulates img/direct-activation.png phosphorylation RPS6KA5 0.601
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HBP1 0.405
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TWIST1 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation KRT8 0.404
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation RPTOR 0.356
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation TP53BP1 0.2
Publications: 1 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation MAPKAPK5 0.606
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation EWSR1 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png MAPK11 0.2
Publications: 1 Organism: Homo Sapiens
Tissue: Kidney
+ up-regulates img/direct-activation.png phosphorylation MAPK11 0.693
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png MAPK11 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ATF2 0.747
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition MAPK11 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png chemical inhibition MAPK11 0.8
Publications: 1 Organism: In Vitro
+ up-regulates img/direct-activation.png chemical activation MAPK11 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png RUNX2 0.287
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation HBA1 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation SMAD2 0.358
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation HBB 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/indirect_inhibition.png MEK1/2 0.458
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition MAPK11 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TP53 0.595
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition MAPK11 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MAPK11 0.424
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation mTORC1 0.334
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation EGFR 0.339
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png chemical inhibition MAPK11 0.8
Publications: 1 Organism: Homo Sapiens