MAPK11 (基因名), Mitogen-activated protein kinase 11 (蛋白名), MK11_HUMAN.
Human MAPK11/ Mitogen-activated protein kinase 11 Recombinant Protein
Mitogen-activated protein kinase p38 beta, Stress-activated protein kinase 2b, p38-2, MAP kinase p38 beta, SAPK2b, MAP kinase 11, PRKM11, SAPK2, SAPK2B
>90% by SDS-PAGE
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50mM NaH2PO4, 500mM NaCl Buffer with 500mM Imidazole, 10%glycerol(PH8.0)
Store at -20°C. (Avoid repeated freezing and thawing.)
Interacts with HDAC3 and DUSP16.
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.
MSGPRAGFYR | QELNKTVWEV | PQRLQGLRPV | GSGAYGSVCS | AYDARLRQKV |
AVKKLSRPFQ | SLIHARRTYR | ELRLLKHLKH | ENVIGLLDVF | TPATSIEDFS |
EVYLVTTLMG | ADLNNIVKCQ | ALSDEHVQFL | VYQLLRGLKY | IHSAGIIHRD |
LKPSNVAVNE | DCELRILDFG | LARQADEEMT | GYVATRWYRA | PEIMLNWMHY |
NQTVDIWSVG | CIMAELLQGK | ALFPGSDYID | QLKRIMEVVG | TPSPEVLAKI |
SSEHARTYIQ | SLPPMPQKDL | SSIFRGANPL | AIDLLGRMLV | LDSDQRVSAA |
EALAHAYFSQ | YHDPEDEPEA | EPYDESVEAK | ERTLEEWKEL | TYQEVLSFKP |
PEPPKPPGSL | EIEQ
"Activation of the novel stress-activated protein kinase SAPK4 by cytokines and cellular stresses is mediated by SKK3 (MKK6); comparison of its substrate specificity with that of other SAP kinases."
"The three-dimensional structure of MAP kinase p38beta: different features of the ATP-binding site in p38beta compared with p38alpha."
"Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors."
"Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles."
"p38-2, a novel mitogen-activated protein kinase with distinct properties."
"Characterization of the structure and function of a new mitogen-activated protein kinase (p38beta)."
"Polymorphisms in innate immunity genes and patients response to dendritic cell-based HIV immuno-treatment."
"Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study."
"Mechanisms and functions of p38 MAPK signalling."
"Activin A induction of erythroid differentiation through MKK6-p38alpha/p38beta pathway is inhibited by follistatin."
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