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Recombinant Human p38 alpha/MAPK14 protein is a Human Full Length protein, in the 1 to 360 aa range, expressed in Escherichia coli, with >95% purity and suitable for SDS-PAGE.

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Images

Key facts

Purity

>95% SDS-PAGE

Expression system

Escherichia coli

Tags

His tag C-Terminus

Applications

SDS-PAGE

Biologically active

No

Amino acid sequence

M S Q E R P T F Y R Q E L N K T I W E V P E R Y Q N L S P V G S G A Y G S V C A A F D T K T G L R V A V K K L S R P F Q S I I H A K R T Y R E L R L L K H M K H E N V I G L L D V F T P A R S L E E F N D V Y L V T H L M G A D L N N I V K C Q K L T D D H V Q F L I Y Q I L R G L K Y I H S A D I I H R D L K P S N L A V N E D C E L K I L D F G L A R H T D D E M T G Y V A T R W Y R A P E I M L N W M H Y N Q T V D I W S V G C I M A E L L T G R T L F P G T D H I N Q L Q Q I M R L T G T P P A Y L I N R M P S H E A R N Y I Q S L T Q M P K M N F A N V F I G A N P L A V D L L E K M L V L D S D K R I T A A Q A L A H A Y F A Q Y H D P D D E P V A D P Y D Q S F E S R D L L I D E W K S L T Y D E V I S F V P P P L D Q E E M E S

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Reactivity data

Application

SDS-PAGE

Reactivity

Reacts

Dilution info

-

Notes

-

Target data

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. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'.(Microbial infection) Activated by phosphorylation by M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma production; phosphorylation is apparent within 15 minute and is inhibited by kinase-specific inhibitors SB203580 and siRNA (PubMed:21586573).

Alternative names

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Recombinant Human p38 alpha/MAPK14 protein is a Human Full Length protein, in the 1 to 360 aa range, expressed in Escherichia coli, with >95% purity and suitable for SDS-PAGE.

Alternative names

Key facts

Purity

>95% SDS-PAGE

Expression system

Escherichia coli

Applications

SDS-PAGE

Accession
Q16539-1
Animal free

No

Species

Human

Concentration
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Storage buffer

pH: 7.9
Constituents: 20% Glycerol (glycerin, glycerine), 0.75% Potassium chloride, 0.316% Tris HCl, 0.0154% (R*,R*)-1,4-Dimercaptobutan-2,3-diol, 0.00584% EDTA

Sequence info

Amino acid sequence

M S Q E R P T F Y R Q E L N K T I W E V P E R Y Q N L S P V G S G A Y G S V C A A F D T K T G L R V A V K K L S R P F Q S I I H A K R T Y R E L R L L K H M K H E N V I G L L D V F T P A R S L E E F N D V Y L V T H L M G A D L N N I V K C Q K L T D D H V Q F L I Y Q I L R G L K Y I H S A D I I H R D L K P S N L A V N E D C E L K I L D F G L A R H T D D E M T G Y V A T R W Y R A P E I M L N W M H Y N Q T V D I W S V G C I M A E L L T G R T L F P G T D H I N Q L Q Q I M R L T G T P P A Y L I N R M P S H E A R N Y I Q S L T Q M P K M N F A N V F I G A N P L A V D L L E K M L V L D S D K R I T A A Q A L A H A Y F A Q Y H D P D D E P V A D P Y D Q S F E S R D L L I D E W K S L T Y D E V I S F V P P P L D Q E E M E S

Accession

Q16539

Protein length

Full Length

Predicted molecular weight

43.3 kDa

Amino acids

1 to 360

Nature

Recombinant

Tags

His tag C-Terminus

Specifications

Form

Liquid

Additional notes

Purified by an affinity column in combination with FPLC chromatography.

General info

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. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.

Post-translational modifications

Dually phosphorylated on Thr-180 and Tyr-182 by the MAP2Ks MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6 in response to inflammatory citokines, 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. PPM1D also mediates dephosphorylation and inactivation of MAPK14 (PubMed:21283629).

Subcellular localisation

Nucleus

Storage

Shipped at conditions

Dry Ice

Appropriate long-term storage conditions

-80°C

Aliquoting information

Upon delivery aliquot

Storage information

Avoid freeze / thaw cycle

Notes

ab82188 contains no detectable proteases, DNase and RNase activity.

Supplementary info

Biological function summary

P38 alpha MAPK14 is a part of a larger mitogen-activated protein kinase (MAPK) complex where it serves to mediate signals from external stressors to the appropriate cellular processes. It is particularly active in its roles involving inflammation and apoptosis regulation. The protein interacts with other members of the MAPK family and additional proteins such as TAB1 to conduct these biological signals efficiently.

Activity summary

P38 alpha also known as MAPK14 is a significant member of the MAP kinase family involved in cellular response to stress signals. This protein has a molecular mass of about 38 kDa and is expressed in various tissues throughout the body. p38 alpha plays an important role in the signal transduction pathways that regulate inflammatory responses and cell differentiation. Its activity is modulated by multiple upstream kinases leading to cell-specific effects that are important for organismal homeostasis.

Pathways

P38 alpha integrates into the p38 MAPK pathway and the NF-kB signaling pathway which are essential for managing cellular stress responses and inflammatory reactions. It closely interacts with other proteins like MKK3 and MKK6 which are directly upstream regulators phosphorylating and activating p38 MAPK14. This intricate connection allows p38 alpha to execute precise regulation within cellular environments.

Associated diseases and disorders

P38 alpha MAPK14 is prominently associated with inflammatory diseases such as rheumatoid arthritis and cardiovascular disorders. In these conditions its aberrant activation or expression can lead to pathological inflammation and tissue damage. Additionally p38 alpha’s connection with TNF-alpha in inflammation highlights its relevance in therapeutic targets for related disorders reflecting the significance of its modulation to potentially mitigate disease progression.

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5 product images

  • SDS-PAGE - Recombinant Human p38 alpha/MAPK14 protein (ab82188), expandable thumbnail

    SDS-PAGE - Recombinant Human p38 alpha/MAPK14 protein (ab82188)

  • Western blot - Recombinant Human p38 alpha/MAPK14 protein (ab82188), expandable thumbnail

    Western blot - Recombinant Human p38 alpha/MAPK14 protein (ab82188)

    This data was developed using the same antibody clone in a different buffer formulation (ab32142).

    All lanes: Western blot - Anti-p38 beta/MAPK11 + p38 alpha/MAPK14 antibody [Y122] (AB32142) at 1/1000 dilution

    Lane 1: Western blot - Recombinant Human p38 beta/MAPK11 protein (AB117219)

    Lane 2: Western blot - Recombinant Human p38 gamma/MAPK12 protein (AB117221)

    Lane 3: Western blot - Recombinant Human p38 delta/MAPK13 protein (AB113869)

    Lane 4: Western blot - Recombinant Human p38 alpha/MAPK14 protein (AB82188)

  • Western blot - Recombinant Human p38 alpha/MAPK14 protein (ab82188), expandable thumbnail

    Western blot - Recombinant Human p38 alpha/MAPK14 protein (ab82188)

    All lanes: Western blot - Anti-p38 delta/MAPK13 + p38 alpha/MAPK14 antibody [M138] (AB31828) at 1/1000 dilution

    Lane 1: Western blot - Recombinant Human p38 beta/MAPK11 protein (AB117219)

    Lane 2: Western blot - Recombinant Human p38 gamma/MAPK12 protein (AB117221)

    Lane 3: Western blot - Recombinant Human p38 delta/MAPK13 protein (AB113869)

    Lane 4: Western blot - Recombinant Human p38 alpha/MAPK14 protein (AB82188)

  • Western blot - Recombinant Human p38 alpha/MAPK14 protein (ab82188), expandable thumbnail

    Western blot - Recombinant Human p38 alpha/MAPK14 protein (ab82188)

    All lanes: Western blot - Anti-p38 alpha/MAPK14 antibody [9F12] (AB59461) at 1/1000 dilution

    Lane 1: Western blot - Recombinant Human p38 beta/MAPK11 protein (AB117219)

    Lane 2: Western blot - Recombinant Human p38 gamma/MAPK12 protein (AB117221)

    Lane 3: Western blot - Recombinant Human p38 delta/MAPK13 protein (AB113869)

    Lane 4: Western blot - Recombinant Human p38 alpha/MAPK14 protein (AB82188)

    Predicted band size: 41 kDa

  • Western blot - Recombinant Human p38 alpha/MAPK14 protein (ab82188), expandable thumbnail

    Western blot - Recombinant Human p38 alpha/MAPK14 protein (ab82188)

    All lanes: Western blot - Anti-p38 beta/MAPK11 antibody [E13-Q] - C-terminal (AB183208) at 1/1000 dilution

    Lane 1: Western blot - Recombinant Human p38 beta/MAPK11 protein (AB117219)

    Lane 2: Western blot - Recombinant Human p38 gamma/MAPK12 protein (AB117221)

    Lane 3: Western blot - Recombinant Human p38 delta/MAPK13 protein (AB113869)

    Lane 4: Western blot - Recombinant Human p38 alpha/MAPK14 protein (AB82188)

    Predicted band size: 41 kDa

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