MAPK11 - Mitogen-activated protein kinase 11 - human protein (Function)
 
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MAPK11 »  Mitogen-activated protein kinase 11   [ EC 2.7.11.24 ]  (MAPK 11)
 
Protein also known as:  Mitogen-activated protein kinase p38 beta (p38b).
Gene name:  MAPK11
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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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  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524] silver  
  • IEAOrtholog Compara
MAP kinase activitydefinition[GO:0004707]  
2
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
2
  • IPIIntAct
GO biological process 
Intracellular signal transductiondefinition[GO:0035556]  
1
  • IDAUniProtKB
Response to stressdefinition[GO:0006950]  
1
  • IDAUniProtKB
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.24: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It requires the following cofactor
Magnesium (By similarity).  
  • CuratedUniProtKB
It is regulated in the following manner
Activated by phosphorylation on threonine and tyrosine by MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 induced by environmental stress. HDAC3 interacts directly and selectively with MAPK11 to repress ATF2 transcriptional activity, and regulate TNF gene expression in LPS-stimulated cells. Inhibited by SB203580 and pyridinyl-imidazole related compounds.  
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  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Amyotrophic lateral sclerosis (ALS)  hsa05014+5600  
Chagas disease (American trypanosomiasis)  hsa05142+5600  
Dopaminergic synapse  hsa04728+5600  
Epithelial cell signaling in Helicobacter pylori infection  hsa05120+5600  
Fc epsilon RI signaling pathway  hsa04664+5600  
GnRH signaling pathway  hsa04912+5600  
Hepatitis C  hsa05160+5600  
Influenza A  hsa05164+5600  
Leishmaniasis  hsa05140+5600  
Leukocyte transendothelial migration  hsa04670+5600  
MAPK signaling pathway  hsa04010+5600  
Neurotrophin signaling pathway  hsa04722+5600  
NOD-like receptor signaling pathway  hsa04621+5600  
Osteoclast differentiation  hsa04380+5600  
Pertussis  hsa05133+5600  
Progesterone-mediated oocyte maturation  hsa04914+5600  
RIG-I-like receptor signaling pathway  hsa04622+5600  
Salmonella infection  hsa05132+5600  
Shigellosis  hsa05131+5600  
T cell receptor signaling pathway  hsa04660+5600  
Toll-like receptor signaling pathway  hsa04620+5600  
Toxoplasmosis  hsa05145+5600  
Tuberculosis  hsa05152+5600  
VEGF signaling pathway  hsa04370+5600  
According to Reactome, this protein belongs to the following pathways:
Cell-Cell communication  REACT_111155  
Cellular responses to stress  REACT_120956  
Developmental Biology  REACT_111045  
Gene Expression  REACT_71  
Immune System  REACT_6900  
Metabolism of RNA  REACT_21257  
Organelle biogenesis and maintenance  REACT_200751  
Signal Transduction  REACT_111102  
TRAF6 Mediated Induction of proinflammatory cytokines  REACT_6782  
 

Keywords

Biological process 
Stress response  definition   [KW-0346]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: MAPK11
GenomeRNAi: 5600
PRO: PR:Q15759
Chemistry
GuidetoPHARMACOLOGY: 1500