P38 map kinase p38 mitogen activated protein kinases. Medical search. Frequent questions

Mitogen-activated protein kinase (MAPK) cascades are essential for eukaryotic cells to integrate and respond to diverse stimuli. (nih.gov)
Finally, we validated a set of full-length proteins harboring docking sites selected in our screens to be authentic MAPK interactors and substrates. (nih.gov)
Persistent activation of the p38 MAPK pathway in muscle satellite cells (muscle stem cells) due to ageing, impairs muscle regeneration. (wikipedia.org)
p38 MAP Kinase (MAPK), also called RK or CSBP (Cytokinin Specific Binding Protein), is the mammalian orthologue of the yeast Hog1p MAP kinase, which participates in a signaling cascade controlling cellular responses to cytokines and stress. (wikipedia.org)
Oxidative stress is the most powerfully specific stress activating p38 MAPK. (wikipedia.org)
The potential of p38 MAPK inhibitors was initially explored within archetypal inflammatory conditions such as rheumatoid arthritis and Crohn's disease, but early studies demonstrated poor clinical efficacy and unacceptable side effects. (medscape.com)
Subsequent clinical trials evaluating different p38 MAPK inhibitor compounds in disease models such as chronic obstructive pulmonary disease (COPD) and atherosclerosis have shown potential clinical efficacy. (medscape.com)
This review aims to provide succinct background information regarding the p38 MAPK signaling pathway, a focus of p38 MAPKs in disease, and a brief summary of relevant preclinical studies. (medscape.com)
It provides a current perspective of the therapeutic potential of p38 MAPK inhibitors in the cardiovascular domain, including safety, tolerability, and pharmacokinetics. (medscape.com)
They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. (nih.gov)
We apply the approach to the dynamic signaling complex formed between the mitogen-activated protein kinase (MAPK) p38α and the intrinsically disordered regulatory domain of the MAPK kinase MKK4. (nih.gov)
The p38 mitogen-activated protein kinase (MAPK) signaling pathway, acting through the downstream kinase MK2, regulates the stability of many proinflammatory mRNAs that contain adenosine/uridine-rich elements (AREs). (birmingham.ac.uk)
Here we show that the p38 MAPK pathway regulates the subcellular localization and stability of TTP protein. (birmingham.ac.uk)
A p38 MAPK inhibitor causes rapid dephosphorylation of TTP, relocalization from the cytoplasm to the nucleus, and degradation by the 20S/26S proteasome. (birmingham.ac.uk)
Hence, continuous activity of the p38 MAPK pathway is required to maintain the phosphorylation status, cytoplasmic localization, and stability of TiP protein. (birmingham.ac.uk)
Furthermore, the extracellular signal-regulated kinase (ERK) pathway synergizes with the p38 MAPK pathway to regulate both stability and localization of TTP. (birmingham.ac.uk)
This effect is independent of kinases that are known to be synergistically activated by ERK and p38 MAPK. (birmingham.ac.uk)
We present a model for the actions of TTP and the p38 MAPK pathway during distinct phases of the inflammatory response. (birmingham.ac.uk)
The p38 MAPK (mitogen-activated protein kinase) pathway contains protein kinases which engage in respond to various extracellular stimuli an intracellular signalling cascade, coordinating the activation of gene transcription, protein synthesis, cell cycle machinery, cell death, and differentiation. (proteinkinase.biz)
The different p38 MAPK family members ( p38α , p38β , p38γ , p38δ ) encoded by different genes show an approximately 60% identical in their amino acid sequence but have different tissue expression patterns. (proteinkinase.biz)
Down-regulation of p38 MAPK is achieved for instance by Wip1, a phosphatase of the PP2C family that can be transcriptionally up-regulated by p53 or by MKPs, a family of dual-specificity protein phosphatases. (proteinkinase.biz)
2010) "Mechanisms and functions of p38 MAPK signalling. (proteinkinase.biz)
Roux PP, Blenis J.,(2004) "ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. (proteinkinase.biz)
The main recognition characteristics of the ATP binding site of p38 mitogen activated protein kinase alpha (p38alpha MAPK) have been explored by a combination of modeling and bioinformatics techniques, making special emphasis in the characteristics of the site that justifies binding specificity with respect to other MAP kinases. (ub.es)
Particularly, we have analyzed the binding mode of a new family of p38 MAPK inhibitors based on the pyridinyl-heterocycle core. (ub.es)
Increasing evidence suggests that enhanced production of reactive oxygen species (ROS) activates the MAP kinases, c-Jun N-terminal protein kinase (JNK) and mitogen-activated protein kinase MAPK (p38). (tau.ac.il)
The pathways involve a triple kinase core cascade comprising the MAP kinase (MAPK), which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPK kinase kinase (MAPKKK or MKKK or MAP3K). (umbc.edu)
There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. (umbc.edu)
Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. (umbc.edu)
Three MAPK proteins, i.e., extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 MAPK are thought to play different roles in chronic inflammatory diseases and homeostasis in the skin ( 6 - 8 ). (spandidos-publications.com)

MKK3 and SEK activate p38 MAP kinase by phosphorylation at Thr-180 and Tyr-182. (wikipedia.org)
Embryoid body (EB) differentiation was evaluated by contracting cardiomyocyte formation, and real-time polymerase chain reaction (RT-PCR) was used for cardiomyocyte-specific and stem-cell-specific gene expression.Acute treatment of mouse embryonic stem (ES) cells with 50 microM Cr(VI) induced the rapid phosphorylation of JNK, p38, and ERK and their respective downstream transcription factors, c-JUN, activating transcription factor-2, and ELK1. (nih.gov)
ERK may be activated by phosphorylation by the dual specificity mitogen-activated kinase kinases, MAP2K1 ( Q02750 , also known as MEK1) and MAP2K2 ( P36507 , also known as MEK2). (guidetopharmacology.org)
p38 may be activated by phosphorylation by the dual specificity mitogen-activated kinase kinases, MAP2K3 ( P46734 , also known as MEK3) and MAP2K6 ( P52564 , also known as SAPKK3). (guidetopharmacology.org)
p38 MAPKs being activated by dual phosphorylation of the Thr-Gly-Tyr in the activation loop sequence by MKKs/MAP2Ks ( MKK6 and MKK3 ). (proteinkinase.biz)
The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. (biossusa.com)
The Bcl-2 family member Bad is a pro-apoptotic protein, and phosphorylation of Bad by cytokines and growth factors promotes cell survival in many cell types. (umn.edu)
Inhibition of mitogen-activated protein (MAP) kinases including ERKs, JNKs, and p38 kinase by the use of their respective dominant negative mutant or a specific inhibitor for MEK1 or p38 kinase, PD98059 or SB202190, resulted in abrogation of UVB-induced phosphorylation of Bad at serine 112. (umn.edu)
Incubation of active MAP kinase members with Bad protein showed serine 112 phosphorylation of Bad by JNK1 only. (umn.edu)
Cells from a Coffin-Lowry syndrome patient (deficient in RSK2) or expressing an N-terminal or C-terminal kinase-dead mutant of MSK1 were defective for UVB-induced serine 112 phosphorylation of Bad. (umn.edu)
Furthermore, MAP kinase pathway-dependent serine 112 phosphorylation was shown to be required for dissociation of Bad from Bcl-X L . These data illustrated that UVB-induced phosphorylation of Bad at serine 112 was mediated through MAP kinase signaling pathways in which JNK1, RSK2, and MSK1 served as direct mediators. (umn.edu)
In human HEK293T cells, YPEL5 silencing enhanced the induction of IFNB1 by pattern recognition receptors and phosphorylation of TBK1/IKBKE kinases, whereas co-immunoprecipitation experiments revealed that YPEL5 interacted physically with IKBKE. (bvsalud.org)
Protein kinase C (PKC) is known to increase non-amyloidogenic alpha-secretase cleavage of APP, producing secreted APP (sAPPalpha), and glycogen synthase kinase (GSK)-3beta is known to increase tau phosphorylation. (ox.ac.uk)
Cross-linking of rituximab induced strong and sustained phosphorylation of the 3 mitogen activated protein (MAP) kinases c-Jun NH2-terminal protein kinase, extracellular signal-regulated kinase, and p38. (ashpublications.org)
In the case of the Jun-dependent transcription, this effect was not due to direct phosphorylation of c-Jun by activated CaM-KIV, since transcription was blocked by a dominant-negative JNK and by two MAP kinase phosphatases. (elsevierpure.com)
Mutation of the phosphorylation site (Thr 196 ) in CaM-KIV, which mediates its activation by CaM-KIV kinase, prevented activation of Elk-1, c-Jun, and ATF2 by the CaM kinase cascade. (elsevierpure.com)
By analysis of the adaptor proteins NCK1 and GRB2 mutants we further show that the negative loop on p38 is mediated by c-ABL phosphorylation at tyrosine 105 of the adaptor protein NCK1, while the phosphorylation at tyrosine 209 of GRB2 down-modulates ERK1/2 and JNKs signaling. (unisi.it)
Classic TGF-β signaling involves the binding of TGF-β to TGF-β type II receptors (TβRIIs), recruitment of type I receptors (TβRIs), transphosphorylation by TβRII kinase, and the subsequent phosphorylation of receptor regulated (R-)Smad2 and Smad3. (springer.com)

The cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), which are both released by activated glial cells, were individually sufficient and necessary for LTP induction via redundant pathways. (jneurosci.org)
21. Regulation of c-Jun N-terminal kinase and p38 kinase pathways in endothelial cells. (nih.gov)
Kyriakis JM, Avruch J. (2001) „Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. (proteinkinase.biz)
The mitogen-activated protein kinase kinase (MAPKK) 1 / MAP kinase cascade is thought to be important for a wide variety of signal transduction pathways ( 2 , 4 , 24 , 25 , 29 , 30 ). (rupress.org)
Notably, exposure of cancer cells to TTFields has been shown to result in immunogenic cell death, which is reflected by damage-associated molecular patterns and the formation of micronuclei that further activate DNA sensor-related inflammatory pathways, indicating the immunomodulatory role for TTFields. (conditionmed.org)
The JNK and p38 pathways were further investigated using specific c-Jun or ATF2-dependent transcriptional assays. (elsevierpure.com)
These results establish a new Ca 2+ -dependent mechanism for regulating MAP kinase pathways and resultant transcription. (elsevierpure.com)
The mitogen-activated protein (MAP) kinase signaling pathways are important mediators of cellular responses to extracellular signals. (umbc.edu)
Besides the canonical TGF-β/Smad pathway, TGF-β can directly activate non-Smad signaling pathways [ 6 , 7 ], including the mitogen activated protein (MAP) kinases. (springer.com)
In addition, mitogen-activated protein kinases (MAPKs) regulate key proinflammatory pathways following stimulation with UV and TNF-α ( 4 , 5 ). (spandidos-publications.com)

As of 2020, losmapimod, a p38 inhibitor, is being investigated for the treatment of facioscapulohumeral muscular dystrophy (FSHD) on the basis of p38 inhibition inhibiting the effects of DUX4. (wikipedia.org)
1995) PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. (guidetopharmacology.org)
1995) A synthetic inhibitor of the mitogen-activated protein kinase cascade. (guidetopharmacology.org)
1998) Identification of a novel inhibitor of mitogen-activated protein kinase kinase. (guidetopharmacology.org)
Figure: Real-time kinetic analysis of kinase inhibitor SB203580 binding to p38α using surface plasmon resonance. (proteinkinase.biz)
2004) "Promyelocytic leukemia is a direct inhibitor of SAPK2/p38 mitogen-activated protein kinase" J Biol Chem. (proteinkinase.biz)
To assess the effects of PBDE-209 on apoptosis, we used the protein kinase Cα (PKCα) inhibitor Gö 6976, the extracellular signal-regulated kinase (ERK) inhibitor PD98059, and tamoxifen. (nih.gov)
Introduction of the p38 inhibitor SB203580 into the system completely blocked signaling downstream of p38, as evidenced by the absence of MAPKAP K2 activity, and significantly reduced the degree of anti-CD20-induced apoptosis. (ashpublications.org)
By treating HUVEC with the specific tyrosine kinase inhibitor STI571 and over-expressing a dominant negative c-ABL mutant, we show that the VEGF-A-activated c-ABL reduces the amplitude of Mitogen-Activated Protein Kinases (ERK1/2, JNKs and p38) activation in a dose-dependent manner by a negative feedback mechanism. (unisi.it)

Here, we screened a proteomic library for sequences interacting with the MAPKs extracellular signal-regulated kinase 2 (ERK2) and p38α, identifying selective and promiscuous docking motifs. (nih.gov)
p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases (MAPKs) that are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell differentiation, apoptosis and autophagy. (wikipedia.org)
p38 mitogen-activated protein kinases (p38 MAPKs) are key signalling molecules that regulate cellular behavior in response to environmental stresses. (medscape.com)
They regulate pro-inflammatory cytokines and therefore p38 MAPKs are implicated in the pathogenesis of many inflammatory-driven conditions, including atherosclerosis. (medscape.com)
Therapeutic inhibition of p38 MAPKs to attenuate inflammation has been the focus of comprehensive research in the last 2 decades, following the discovery of p38α as the molecular target of pyrindinyl imidazole compounds, which suppress the cytokines tumor necrosis factor-α and interleukin-1. (medscape.com)
Within this context, inhibition of p38 mitogen-activated protein kinases (MAPKs) to attenuate inflammation is a prospective therapeutic target worthy of further consideration. (medscape.com)
p38 MAPKs are key signaling molecules in cellular responses to external stresses and regulation of proinflammatory cytokines, and are thus implicated in inflammatory mechanisms of disease, including those affecting the heart and vasculature. (medscape.com)
Mitogen-activated protein kinase 1 (MAPK1/MEK1) belongs to the MAPKs family. (oncotarget.com)

Therefore, we have created descriptors for the three major subclasses: Extracellular Signal-Regulated MAP Kinases, JNK Mitogen-Activated Protein Kinases, and p38 Mitogen-Activated Protein Kinases. (nih.gov)

Distinct contributions of JNK and p38 to chromium cytotoxicity and inhibition of murine embryonic stem cell differentiation. (nih.gov)
40. Dexamethasone suppresses monocyte chemoattractant protein-1 production via mitogen activated protein kinase phosphatase-1 dependent inhibition of Jun N-terminal kinase and p38 mitogen-activated protein kinase in activated rat microglia. (nih.gov)

These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. (nih.gov)
Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. (nih.gov)
33. Overexpression of mitogen-activated protein kinase phosphatases MKP1, MKP2 in human breast cancer. (nih.gov)

The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. (nih.gov)
23. Insulin regulates MAP kinase phosphatase-1 induction in Hirc B cells via activation of both extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK). (nih.gov)
24. Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase. (nih.gov)
26. Feedback regulation of Raf-1 and mitogen-activated protein kinase (MAP) kinase kinases 1 and 2 by MAP kinase phosphatase-1 (MKP-1). (nih.gov)
27. Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1. (nih.gov)
28. Parathyroid hormone-related protein induces insulin expression through activation of MAP kinase-specific phosphatase-1 that dephosphorylates c-Jun NH2-terminal kinase in pancreatic beta-cells. (nih.gov)
30. Mitogen-activated protein kinase phosphatase-1 is overexpressed in non-small cell lung cancer and is an independent predictor of outcome in patients. (nih.gov)
35. Catalytic activation of mitogen-activated protein (MAP) kinase phosphatase-1 by binding to p38 MAP kinase: critical role of the p38 C-terminal domain in its negative regulation. (nih.gov)
36. Hyperosmotic induction of the mitogen-activated protein kinase phosphatase MKP-1 in H4IIE rat hepatoma cells. (nih.gov)
37. Mitogen-activated protein kinase phosphatase 1 is overexpressed in prostate cancers and is inversely related to apoptosis. (nih.gov)
It has recently been reported that microtubule depolymerization by nocodazole treatment can block exit from mitosis in the extracts if enough sperm nuclei are present, and that the addition of MAP kinase- specific phosphatase MKP-1 overcomes this spindle assembly checkpoint, suggesting the involvement of MAP kinase in the checkpoint signal transduction. (rupress.org)
In the absence of depolarization, CaM-KK c transfection had no effect on Elk-dependent transcription of a luciferase reporter gene, whereas CaM-KIV c alone or in combination with CaM-KK c gave 7- to 10-fold and 60- to 80-fold stimulations, respectively, which were blocked by mitogen-activated protein (MAP) kinase phosphatase cotransfection. (elsevierpure.com)

p38 inhibitors are being sought for possible therapeutic effect on autoimmune diseases and inflammatory processes, e.g. pamapimod. (wikipedia.org)
2. Davies SP, Reddy H, Caivano M, Cohen P. (2000) Specificity and mechanism of action of some commonly used protein kinase inhibitors. (guidetopharmacology.org)
Based on SB203580 , one of the first discovered p38α inhibitors structurally diverse p38α and p38β inhibitors have been developed with both enhanced potency and specificity. (proteinkinase.biz)
We provide our Kinascreen services to kinetically characterize small molecule kinase inhibitors for all p38 isoforms (p38α, p38β, p38γ and p38δ) in their phosphorylated (activated) and unphosphorylated (non-activated) state. (proteinkinase.biz)
Addition of PD98059 and SB202190, inhibitors of ERK and p38, respectively, decreased vanadate-induced S phase arrest, reduced p21 levels, restored activation of p-cdk2, and decreased p53 activity. (cdc.gov)

Upstream factors and downstream targets of p38α have been identified in the past by conventional methods such as coimmunoprecipitation. (edu.au)
Gene ontology analysis confirms known upstream and downstream factors in the p38 MAP kinase cascade (e.g. (edu.au)
However, activated RSK2 and MSK1, downstream kinases of ERKs and p38 kinase, respectively, also phosphorylated Bad at serine 112 in vitro. (umn.edu)

Substrates of the encoded protein include the transcription factor ATF2 and the microtubule dynamics regulator stathmin. (nih.gov)
Upon activation p38 MAP kinases can phosphorylate substrates on Ser-Pro or Thr-Pro motifs on MSK1 and 2, which directly phosphorylate the transcription factors CREB , ATF1 , or cytosolic proteins such as phospholipase A2, Bcl-2 family proteins and cyclins . (proteinkinase.biz)
The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response. (biossusa.com)
They are dual specificity enzymes that phosphorylate threonine and tyrosine residues within the activation loop of their MAP kinase substrates [ 9 ]. (oncotarget.com)
PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. (umbc.edu)

In Xenopus laevis , for example, this classical MAP kinase cascade has been shown to play a crucial role in meiotic cell cycles during oocyte maturation, metaphase arrest of unfertilized eggs, and early embryonic development ( 5 , 7 , 9 - 13 , 15 - 18 , 26 , 32 ). (rupress.org)
However, the role of the MAP kinase cascade in mitotic cell cycles has been poorly understood. (rupress.org)
These results suggest that the ceroid/lipofuscin which form in microglia activate the p38 MAP kinase cascade through the increased intracellular generation of ROS in CD-/- mice. (elsevierpure.com)
The activated p38 MAP kinase cascade then promotes the expression of iNOS and CAT-2, thereby inducing the overproduction of NO. (elsevierpure.com)
To investigate whether the Ca 2+ -dependent activation of mitogen-activated protein kinases (ERK, JNK, and p38) might be mediated by the CaM kinase cascade, we have transfected PC12 cells, which lack CaM-KIV, with constitutively active mutants of CaM kinase kinase and/or CaM-KIV (CaM-KK c and CaM-KIV c , respectively). (elsevierpure.com)

Dishevelled regulates the metabolism of amyloid precursor protein via protein kinase C/mitogen-activated protein kinase and c-Jun terminal kinase. (ox.ac.uk)
Regulates mitogenic signal transduction by dephosphorylating both Thr and Tyr residues on MAP kinases ERK1 and ERK2. (nih.gov)
HN - 2006(1998) MH - Activating Transcription Factor 1 UI - D051697 MN - D12.776.260.108.61.500 MN - D12.776.930.127.61.500 MS - An activating transcription factor that regulates expression of a variety of genes including C-JUN GENES and TRANSFORMING GROWTH FACTOR BETA2. (nih.gov)

22. Correlation between sustained c-Jun N-terminal protein kinase activation and apoptosis induced by tumor necrosis factor-alpha in rat mesangial cells. (nih.gov)
Objective: In this study we investigated the effects of PBDE-209, a deca-PBDE, on the regulation of growth and apoptosis of breast, ovarian, and cervical cancer cells as well as the underlying protein alterations. (nih.gov)
These results demonstrate that cross-linking of rituximab bound to CD20 on freshly isolated B-CLL cells induces apoptosis through a signaling pathway that is dependent on p38 MAP-kinase activation. (ashpublications.org)

Similar to the SAPK/JNK pathway, p38 MAP kinase is activated by a variety of cellular stresses including osmotic shock, inflammatory cytokines, lipopolysaccharides (LPS), ultraviolet light, and growth factors. (wikipedia.org)

The encoded protein is a p38 MAP kinase and is activated by proinflammatory cytokines and cellular stress. (nih.gov)
TLRs activate innate immune defense reactions, such as the release of inflammatory cytokines, but increasing evidence supports an additional critical role for TLRs in orchestrating the development of adaptive immune responses. (biomedcentral.com)
This kinase is activated by various environmental stresses and proinflammatory cytokines. (biossusa.com)

Sequences specific for p38α had high net charge and lysine content, and selective binding depended on a pair of acidic residues unique to the p38α docking interface. (nih.gov)

The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. (umbc.edu)

On the basis of immunoprecipitation experiments, in vitro kinase assay and RNA interference, we demonstrate that VEGF-A induces the c-ABL kinase activity through the VEGF Receptor-2 /Phosphatidylinositol-3-Kinase pathway. (unisi.it)

In addition, we show that strong activation of MAP kinase by the addition of a constitutively active MAP kinase kinase kinase in the absence of sperm nuclei and nocodazole, induced mitotic arrest in the extracts. (rupress.org)

Nitric oxide (NO) and peroxynitrite, which are produced by activated microglia, are responsible for accelerated neurodegeneration in cathepsin D-deficient (CD-/-) mice. (elsevierpure.com)
To elucidate the mechanisms by which microglia are initially activated in CD-/- mice, we analyzed the possible relationship between lysosomal storage and microglial activation. (elsevierpure.com)
Furthermore, activated microglia, which are often accumulating subunit c and ceroid/lipofuscin, showed proliferation activity and an activation of p38 mitogen-activated protein (MAP) kinase. (elsevierpure.com)
In these pepstatin A-treated microglia, both an increased generation of the intracellular reactive oxygen species (ROS) and an activation of p38 MAP kinase were observed. (elsevierpure.com)

Dysregulated NF-κB activity can activate genes that cause cancer cell survival, and can also activate genes that facilitate cancer cell metastasis to other tissues. (wikipedia.org)
Gene-mapping studies have revealed that TLR genes are dispersed throughout the mammalian genome. (biomedcentral.com)
DNA sequence comparisons of genes encoding Toll-related proteins in Drosophila , reptiles, birds and in mammals have revealed that the genes are well conserved and have evolved independently from a common ancestor gene [ 8 ]. (biomedcentral.com)
Exposure to UV irradiation can activate various oncogenes and inactivate many tumor suppressor genes. (aacrjournals.org)
This domain occurred 427 times on human genes ( 994 proteins). (umbc.edu)

First identified on the basis of sequence similarity with the Drosophila protein Toll, TLRs are members of an ancient superfamily of proteins, which includes related proteins in invertebrates and plants. (biomedcentral.com)
CB1 and CB2 are members of a superfamily of seven-transmembrane-spanning (7-TM) receptors, which have a protein structure defined by an array of seven-membrane-spanning helices with intervening intracellular loops and a COOH-terminal domain that can associate with G proteins. (aacrjournals.org)

It is thought to do this by modulating the expression or activity of ARE-binding proteins that regulate mRNA turnover. (birmingham.ac.uk)
AN - coordinate IM with ADENOMA (IM) HN - 2006 BX - Corticotroph Adenoma BX - Pituitary Adenoma, ACTH-Secreting BX - Pituitary Corticotropin-Secreting Adenoma MH - Actin Capping Proteins UI - D051344 MN - D5.750.78.730.32 MN - D12.776.220.525.32 MS - Actin capping proteins are cytoskeletal proteins that bind to the ends of ACTIN FILAMENTS to regulate actin polymerization. (nih.gov)

Mechanistically, MEK1 signaling keeps SIRT1 protein stabilization through activating SIRT1 ubiquitination, which inhibits proteasomal degradation. (oncotarget.com)

Activated p38 MAP kinase has been shown to phosphorylate and activate MAPKAP kinase 2 and to phosphorylate the transcription factors ATF2, Mac, MEF2, and p53. (wikipedia.org)

Protein kinases (PKs), MAP kinase kinase (MAPKK) subfamily, catalytic (c) domain. (umbc.edu)

Suitable for kinase molecule interaction analyses using SPR , as substrate for kinase activity assays and for western blot analyses. (proteinkinase.biz)

These results define an extensive network of interactions of p38α in cells and new direct molecular targets of MAP kinase p38α in gene regulation and the DNA damage response. (edu.au)
MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. (nih.gov)
The regulation of both subcellular localization and protein stability is dependent on MK2 and on the integrity of serines 52 and 178. (birmingham.ac.uk)
The members of the DNA Repair Interest Group perform research in areas including DNA repair enzymology and fine structure, mutagenesis, gene and cell cycle regulation, protein structure, and human disease. (nih.gov)

To examine the possible role of MAP kinase in the in vitro cell cycle, we depleted the extracts of MAP kinase by using anti- Xenopus MAP kinase antibody. (rupress.org)
Like in the mock-treated extracts, the periodic activation and deactivation of MPF occurred normally in the MAP kinase-depleted extracts, suggesting that MAP kinase is dispensable for the normal M phase entry and exit in vitro. (rupress.org)
Therefore, activation of MAP kinase alone is sufficient for inducing the mitotic arrest in vitro. (rupress.org)

Deficiency in this protein induces a rare autosomal-recessive disease called AUTOIMMUNE POLYENDOCRINOPATHY-CANDIDIASIS-ECTODERMAL DYSTROPHY. (nih.gov)

We furthermore identify a cluster of zinc finger (ZnF) domain-containing proteins that is significantly enriched among proximity-labeled interactors and is involved in gene transcription and DNA damage response. (edu.au)
The protein product of proto-oncogene RAS can increase activity of p38, and thereby cause excessively high activity of transcription factor NF-κB. (wikipedia.org)

These phosphorylated intermediates at the stress-activated pathway induce expression of matrix metalloproteinases (MMPs), leading to inflammatory responses and pathological damages involved in the etiology of multiple sclerosis (MS). Here we report that N-acetylcysteine amide (AD4) crosses the blood-brain barrier (BBB), chelates Cu 2+ , which catalyzes free radical formation, and prevents ROS-induced activation of JNK, p38 and MMP-9. (tau.ac.il)

Biotinylated protein is not phosphorylated and activated by MKKs. (proteinkinase.biz)

Mitogen-Activated Protein Kinases: A large number of distinct Mitogen-activated protein kinase isoenzymes are currently being discussed in the literature. (nih.gov)

Mitogen-activated protein (MAP) kinase signaling is central to multiple cellular responses and processes. (edu.au)

We thus found that the Ypel5 gene (contained in a locus linked to a network of ISGs in mice) is a negative regulator of IFNB1 production and innate immune responses that interacts functionally and physically with TBK1/IKBKE kinases. (bvsalud.org)

HN - 2024 BX - Aflatoxicosis BX - Aflatoxin Toxicity MH - AIRE Protein UI - D000096927 MN - D12.776.930.123 MS - A transcriptional regulator primarily expressed in medullary thymic epithelial cells. (nih.gov)

38. Activated Ki-Ras suppresses 12-O-tetradecanoylphorbol-13-acetate-induced activation of the c-Jun NH2-terminal kinase pathway in human colon cancer cells. (nih.gov)
A marked attenuation of UVB-induced activation of mitogen-activated protein kinases and nuclear factor- κB was associated with CB1/2 deficiency. (aacrjournals.org)
In Xenopus laevis egg cell cycle extracts that mimic early embryonic cell cycles, activation of MAP kinase and MAP kinase kinase occurs in M phase, slightly behind that of maturation promoting factor. (rupress.org)
In Xenopus unfertilized eggs which are arrested at the second meiotic metaphase, MAP kinase is fully activated, whereas in somatic or early embryonic cell cycles marked activation of MAP kinase at M phase has not been detected, although several reports observed the existence of an activated MAP kinase or an activated MAP kinase-like molecule in M phase ( 14 , 31 ). (rupress.org)
These receptors, like the activation of TLR4 by lipopolysaccharide (LPS), activate MAP kinases and a proinflammatory response ultimately. (vaggi.org)
5 min) activation of Ca 2+ /calmodulin-dependent protein kinase IV (CaM-KIV), as well as activation of c-Jun N-terminal kinase (JNK). (elsevierpure.com)
Bone morphogenetic proteins (BMPs) signal specific BMP type I and type II receptors, and stimulate the activation of R-Smad1, 5 and 8. (springer.com)

We show here that the spindle assembly checkpoint mechanism cannot operate in the MAP kinase-depleted extracts. (rupress.org)

But, adding recombinant Xenopus MAP kinase to the MAP kinase-depleted extracts restored the spindle assembly checkpoint. (rupress.org)

Fluorescence imaging and coimmunoprecipitation with overexpressed p38α in cells supports an interaction of p38α with ZnF protein XPA, a key factor in the DNA damage response, that is promoted by UV irradiation. (edu.au)
Intrinsically disordered proteins (IDPs) display a large number of interaction modes including folding-upon-binding, binding without major structural transitions, or binding through highly dynamic, so-called fuzzy, complexes. (nih.gov)
Our study demonstrates that MKK4 employs a subtle combination of interaction modes in order to bind to p38α, leading to a complex displaying significantly different dynamics across the bound regions. (nih.gov)
Proteolytic cleavage, interaction with integrins, or pH changes in the local environment activate latent TGF-β [ 4 ]. (springer.com)

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase. (umbc.edu)

Structural features of human members of the TLR protein family and the archetypal Drosophila Toll protein. (biomedcentral.com)

31. Serotonergic repression of mitogen-activated protein kinase control of the calcitonin gene-related peptide enhancer. (nih.gov)
From NCBI Gene: This gene encodes a member of the mitogen-activated protein (MAP) kinase family. (nih.gov)
The protein encoded by this gene is a member of the MAP kinase family. (biossusa.com)
Description of the protein which includes the UniProt Function and the NCBI Gene Summary. (nih.gov)

Saklatvala J (2004) "The p38 MAP kinase pathway as a therapeutic target in inflammatory disease" Curr Opin Pharmacol. (proteinkinase.biz)

Anatomy19

Organisms8

Chemicals and Drugs172

Analytical, Diagnostic and Therapeutic Techniques and Equipment13

Phenomena and Processes40

Information Science3

MAPK30

Phosphorylation18

Pathways10

Inhibitor9

MAPKs8

Extracellular Signal-1

Inhibition2

Phosphatases3

Phosphatase12

Inhibitors5

Downstream3

Substrates5

Cascade5

Regulates3

Apoptosis3

SAPK1

Cytokines3

Residues1

Serine1

Phosphatidylinositol-3-Kina1

Active MAP kinase1

Microglia4

Genes5

Superfamily2

Regulate2

MEK11

Phosphorylate the transcription factors1

Subfamily1

Substrate1

Regulation4

Vitro3

Induces1

Transcription2

Stress-activated1

MKKs1

Distinct1

Cellular responses1

Responses1

20241

Activation7

Mechanism1

Recombinant1

Interaction4

Catalytic1

Drosophila1

Gene4

Therapeutic target1