抗体

抗磷酸化Thr180/Tyr182 p38 MAPK

MBS502096

0.1毫升

345美元

多克隆

兔

未共轭

磷酸化

人类, 大鼠

免疫印迹, 免疫组化

抗体

抗磷酸化Thr180/Tyr182 p38 MAPK

p38 MAPK(Thr180/Tyr182)

Mitogen-activated protein kinase 14; Mitogen-activated protein kinase 14; mitogen-activated protein kinase 14; MAPK 14; MAP kinase 2; MAP kinase 14; p38alpha Exip; p38 MAP kinase; MAP kinase Mxi2; reactive kinase; MAP kinase p38 alpha; Csaids binding protein; MAX-interacting protein 2; stress-activated protein kinase 2A; mitogen-activated protein kinase 14A; p38 mitogen activated protein kinase; mitogen-activated protein kinase p38 alpha; cytokine-supressive anti-inflammatory drug binding protein; cytokine suppressive anti-inflammatory drug binding protein; mitogen activated protein kinase 14; CRK1; Mitogen-activated protein kinase p38 alpha

MAPK14

Mapk14; Mapk14; RK; Hog; p38; CRK1; CSBP; Exip; Mxi2; CSPB1; Csbp1; Csbp2; Prkm14; Prkm15; Sapk2A; p38Hog; p38alpha; Csbp1; Csbp2; MAP kinase 14; MAPK 14

MK14_RAT

多克隆

兔

人类

360

Specific for the ~39k p38 MAPK protein phosphorylated at Thr180/Tyr182. Immunolabeling is blocked by preadsorption of the antibody with the phosphopeptide used as antigen but not by the corresponding dephosphopeptide.

Affinity Purified (Prepared from rabbit serum by affinity purification via sequential chromatography on phospho- and dephosphopeptide affinity columns.)

100 ul in 10 mM HEPES (pH 7.5), 150 mM NaCl, 100 ug per ml BSA and 50% glycerol. Adequate amount of material to conduct 10-mini Western Blots.

For long term storage -20 degree C is recommended. Stable at -20 degree C for at least 1 year.

免疫印迹(免疫印迹), 免疫组化(免疫组化)

Quality Control: Western blots performed on each lot. WB: 1:1000. IHC: 1:250

Antigen: Phosphopeptide corresponding to amino acid residues surrounding the phospho-Thr180 and phospho-Tyr182 of rat p38 MAPK. Immunogen Information: Synthetic phospho-peptide corresponding to amino acid residues surrounding Thr180/Tyr182 conjugated to KLH. Immunogen Species: Rat

Reactivity Assumed Based on 100% Sequence Homology: Bovine, canine, chicken, mouse, non-human primates, rat and zebra fish. Species Reactivity Note: The antibody has been directly tested for reactivity in Western blots with human tissue. It is anticipated that the antibody will also react with bovine, canine, chicken, mouse, non-human primates, rat and zebra fish based on the fact that these species have 100% homology with the amino acid sequence used as antigen. Biological Significance: The three Mitogen-Activated Protein Kinases (MAPKs) are evolutionarily conserved protein kinases that control a vast array of cellular processes. p38 MAPK is one of these kinases and it is activated by both inflammatory cytokines and by stress (Johnson and Lapadat, 2002; Shi and Gaestel, 2002). The p38 MAPK is thought to be particularly important in diseases like asthma and autoimmunity but it also plays important roles in the stress response of the nervous system (Philip and Armstead, 2003; Ying et al., 2002). Like the other MAPKs, p38 is activated by a dual specificity kinase that phosphorylates Thr180 and Tyr182 (Lin et al., 1995).

亲和纯化兔多克隆抗体

Johnson GL, Lapadat R (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298:1911-1912. Lin A, Minden A, Martinetto H, Claret F-X, Lange-Carter C, Mercurio F, Johnson GL, Karin M (1995) Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. Science 268:286-290. Philip S, Armstead WM (2003) Differential role of PTK, ERK and p38 MAPK in superoxide impairment of NMDA cerebrovasodilation. Brain Res 979:98-103. Shi Y, Gaestel M (2002) In the cellular garden of forking paths: How p38 MAPKs signal for downstream assistance. Biol Chem 383:1519-1536. Ying SW, Futter M, Rosenblum K, Webber MJ, Hunt SP, Bliss TVP, Bramham CR (2002) Brain-derived neurotrophic factor induces long-term potentiation in intact adult hippocampus: Requirement for ERK activation coupled to CREB and upregulation of Arc synthesis. J Neurosci 22:1532-1540.

2499601

P70618.3

P70618

39

ADP Signalling Through P2Y Purinoceptor 1 Pathway (935731); Activated TLR4 Signalling Pathway (936709); Activation Of The AP-1 Family Of Transcription Factors Pathway (936691); Adrenergic Signaling In Cardiomyocytes Pathway (908278); Adrenergic Signaling In Cardiomyocytes Pathway (909696); Amyotrophic Lateral Sclerosis (ALS) Pathway (83491); Amyotrophic Lateral Sclerosis (ALS) Pathway (511); B Cell Receptor Signaling Pathway (198486); CDO In Myogenesis Pathway (936293); Cell-Cell Communication Pathway (936637)

mitogen-activated protein kinase; involved in intracellular signalling, inhibition of apoptosis and gene activation [RGD, Feb 2006]

Function: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 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. 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. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. 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. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. 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. Another p38 MAPK substrate is 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. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Phosphorylates S100A9 at 'Thr-113' . By similarity. Catalytic activity: ATP + a protein = ADP + a phosphoprotein. Cofactor: Magnesium . By similarity. Enzyme regulation: Activated by cell stresses such as DNA damage, heat shock, osmotic shock, anisomycin and sodium arsenite, as well as pro-inflammatory stimuli such as bacterial lipopolysaccharide (LPS) and interleukin-1. Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6, and potentially also MAP2K4/MKK4, as well as by TAB1-mediated autophosphorylation. MAPK14 phosphorylated on both Thr-180 and Tyr-182 is 10-20-fold more active than MAPK14 phosphorylated only on Thr-180, whereas MAPK14 phosphorylated on Tyr-182 alone is inactive. whereas Thr-180 is necessary for catalysis, Tyr-182 may be required for auto-activation and substrate recognition. Phosphorylated at Tyr-323 by ZAP70 in an alternative activation pathway in response to TCR signaling in T-cells. This alternative pathway is inhibited by GADD45A. Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. Specifically inhibited by the binding of pyridinyl-imidazole compounds, which are cytokine-suppressive anti-inflammatory drugs (CSAID). SB203580 is an inhibitor of MAPK14 . By similarity. Subunit structure: Binds to a kinase interaction motif within the protein tyrosine phosphatase, PTPRR . By similarity. This interaction retains MAPK14 in the cytoplasm and prevents nuclear accumulation . By similarity. Interacts with SPAG9 and GADD45A, CDC25B, CDC25C, DUSP1, DUSP10, DUSP16, NP60, SUPT20H and TAB1 . By similarity. Interacts with casein kinase II subunits CSNK2A1 and CSNK2B . By similarity. Subcellular location: Cytoplasm . By similarity. Nucleus . By similarity. Domain: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. Post-translational modification: Dually phosphorylated on Thr-180 and Tyr-182 by the MAP2Ks MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6 in response to inflammatory cytokines, environmental stress or growth factors, which activates the enzyme. Dual phosphorylation can also be mediated by TAB1-mediated autophosphorylation. TCR engagement in T-cells also leads to Tyr-323 phosphorylation by ZAP70. Dephosphorylated and inactivated by DUPS1, DUSP10 and DUSP16 . By similarity.Acetylated at Lys-53 and Lys-152 by KAT2B and EP300. Acetylation at Lys-53 increases the affinity for ATP and enhances kinase activity. Lys-53 and Lys-152 are deacetylated by HDAC3 . By similarity.Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway . By similarity. Sequence similarities: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.Contains 1 protein kinase domain.

0.1毫升

345美元