P38B 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. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Highest levels in the brain and heart. Also expressed in the placenta, lung, liver, skeletal muscle, kidney and pancreas. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: CMGC group; EC 2.7.11.24; Kinase, protein; MAPK family; MAPK/p38 subfamily; Protein kinase, CMGC; Protein kinase, Ser/Thr (non-receptor); p38 subfamily
Chromosomal Location of Human Ortholog: 22q13.33
Cellular Component:  cytosol; nucleoplasm
Molecular Function:  ATP binding; MAP kinase activity; protein binding; protein serine/threonine kinase activity
Biological Process:  activation of MAPK activity; cellular response to interleukin-1; cellular response to virus; negative regulation of cardiac muscle cell proliferation; positive regulation of gene expression; positive regulation of interleukin-12 secretion; positive regulation of muscle cell differentiation; Ras protein signal transduction; regulation of DNA-binding transcription factor activity; regulation of signal transduction by p53 class mediator; stress-activated MAPK cascade; vascular endothelial growth factor receptor signaling pathway
Reference #:  Q15759 (UniProtKB)
Alt. Names/Synonyms: MAP kinase 11; MAP kinase p38 beta; MAPK 11; MAPK11; Mitogen-activated protein kinase 11; Mitogen-activated protein kinase p38 beta; mitogen-activated protein kinase p38-2; MK11; p38-2; p38b; p38Beta; P38BETA2; PRKM11; SAPK2; SAPK2B; Stress-activated protein kinase 2; stress-activated protein kinase-2; stress-activated protein kinase-2b
Gene Symbols: MAPK11
Molecular weight: 41,357 Da
Basal Isoelectric point: 5.56  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis  |  B Cell Receptor Signaling  |  NF-kB Signaling  |  Phospholipase Signaling  |  Regulation of P38 MAPKs  |  T Cell Receptor Signaling  |  TGF-ß Signaling  |  Toll-Like Receptor Signaling  |  Translation: eIF4E and p70S6K
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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P38B

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Cross-references to other databases:  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  InnateDB