Utilizing a genetic screen in the yeast Saccharomyces cerevisiae, we identified a novel autoactivation region in mammalian MEK1 that is involved in binding the specific MEK inhibitor, PD 184352. The genetic screen is possible due to the homology between components of the yeast pheromone response pathway and the eukaryotic Raf-MEK-ERK signaling cascade. Using the FUS1::HIS3 reporter as a functional readout for activation of a reconstituted Raf-MEK-ERK signaling cascade, randomly mutagenized MEK variants that were insensitive to PD 184352 were obtained. Seven single-base-change mutations were identified, five of which mapped to kinase subdomains III and IV of MEK. Of the seven variants, only one, a leucine-to-proline substitution at amino acid 115 (Leu115Pro), was completely insensitive to PD 184352 in vitro (50% inhibitory concentration ,10 μM). However, all seven mutants displayed strikingly high basal activity compared to wild-type MEK. Overexpression of the MEK variants in HEK293T cells ...

Zama T., Aoki R., Kamimoto T., Inoue K., Ikeda Y., Hagiwara M.. Stress-activated protein kinase (SAPK) pathway-regulating phosphatase 1 (SKRP1) has been identified as a member of the mitogen-activated protein kinase (MAPK) phosphatase (MKP) family that interacts physically with the MAPK kinase (MAPKK) MKK7, a c-Jun N-terminal kinase (JNK) activator, and inactivates the MAPK JNK pathway. Although these findings indicated that SKRP1 contributes to the precise regulation of JNK signaling, it remains to be elucidated how SKRP1 is integrated into this pathway. We report that SKRP1 also plays a scaffold role for the JNK signaling, judged by the following observations. SKRP1 selectively formed the stable complexes with MKK7 but not with MKK4 and biphasically regulated the MKK7 activity and MKK7-induced gene transcription in vivo. Co-precipitation analysis between SKRP1 and MKK7-activating MAPKK kinases (MAPKKKs) revealed that SKRP1 also interacted with the MAPKKK, apoptosis signal-regulating kinase 1 ...

Glucocorticoids prevent the adverse proasthmatic effects of prolonged LABA exposure on airway responsiveness as a result of glucocorticoid-induced upregulation of mitogen-activated protein kinase phosphatase 1, which inhibits proasthmatic ERK1/2 signaling in the LABA-exposed ASM.

Mitogen-activated protein MAP kinases are key signal-transducing enzymes that are activated by a wide range of extracellular stimuli. They are responsible for the induction of a number of cellular responses, such as changes in gene expression, proliferation, differentiation, cell cycle arrest and ap …

We next addressed the question of whether Pmp1 modulated the level of Pmk1 tyrosine phosphorylation in vivo. As shown in Figure 8B, Pmk1 tyrosine phosphorylation was significantly enhanced in Δpmp1 cells, but almost completely abolished in cells overproducing Pmp1. In sharp contrast, overproduction of catalytically inactive Pmp1C158S resulted in an elevated level of tyrosine‐phosphorylated Pmk1 (Figure 8B).. With the goal of establishing that Pmk1 MAP kinase is a direct target of Pmp1 phosphatase in vivo, we then asked whether Pmp1 and Pmk1 physically interacted. For this, hemagglutinin (HA) epitope‐tagged Pmk1 and GST-Pmp1, GST-Pmp1C158S or unfused GST were co‐expressed in S.pombe, followed by precipitation with glutathione beads. Beads were washed thoroughly and analyzed by immunoblotting using anti‐HA and anti‐GST antibodies. The results obtained (Figure 8C) clearly show that HA‐tagged Pmk1 co‐precipitates with GST-Pmp1, but not with unfused GST. A much larger amount of Pmk1 ...

TOPK (T-lymphokine-activated killer cell-originated protein kinase, also known as PBK or PDZ-binding kinase) is a Ser/Thr protein kinase that is highly expressed in many types of human cancer, including breast and lung cancers. TOPK is included in the consensus stemness ranking signature gene list that is up-regulated in cancer stem cell-enriched tumors and is associated with poor prognosis in multiple types of cancer.. TOPK/PBK is an oncogenic kinase upregulated in most human cancers. TOPK is important for mitotic cell division and that phosphorylation by Cdk1 is needed for its activation.. TOPK, a member of the MEK3/6-related MAPKK family, is expressed in a wide range of proliferating cells and tissues, including cancer cells and testis. TOPK negatively regulates the activity of p38α by phosphorylating the p38α-specific phosphatase MKP1 and enhancing the stability of MKP1. The MAPK phosphatase MKP1, an archetypal member of the MKP family, plays a pivotal role in the deactivation of p38 ...

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Shop Probable rhodanese domain-containing dual specificity protein phosphatase ELISA Kit, Recombinant Protein and Probable rhodanese domain-containing dual specificity protein phosphatase Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.

Dual specificity protein phosphatase; active with phosphotyrosine, phosphoserine and phosphothreonine residues. The highest relative activity is toward ERK1.

The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which is associated with cellular proliferation and differentiation. 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. This gene product is localized to the nucleus and binds directly to RNA and splicing factors, and thus it is suggested to participate in nuclear mRNA metabolism. [provided by RefSeq, Sep 2008 ...

Purpose: : Dual specificity mitogen-activated protein kinase (MAPK) phosphatases (DUSPs) negatively regulate MAPK activity in mammalian cells. The purpose of this study was to analyze endogenous and fibroblast growth factor (FGF) regulation of DUSP expression in ocular tissues. Methods: : DUSP expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) on RNA isolated from eyes of new born mice. Tissue-specific expression of DUSPs in wild type and in transgenic mice that expressed either FGF-7, -8, -9 or -10 in their lens fiber cells was analyzed by in situ hybridization. Expression analyses were performed on ocular sections of formalin-fixed paraffin embedded heads of embryos or pups. Results: : RT-PCR results suggested that all 12 members of the DUSP family (DUSP1-10, 16A1 and 16B1) were expressed in the murine eye at post natal day (P1). In addition, expression of Styx, a related member of the DUSP family, was also detected in ocular tissues. In situ hybridization ...

Mouse anti Human DUSP5 antibody, clone 4C8 recognizes human dual specificity protein phosphatase 5, also known as DUSP5 or Dual specificity

Dual specificity protein phosphatase 1 (367 aa, ~39 kDa) is encoded by the human DUSP1 gene. This protein plays a role in the dephosphorylation of mitogen-activated protein kinase 1.

DUSP12 is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both…

Read mVH1, a dual-specificity phosphatase whose expression is cell cycle regulated, Mammalian Genome on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.

Nanoparticle drug delivery systems have already been found in the clinic because the early 1990s. Since 2016, the amount of clinical studies of VYXEOS provides XAV 939 pontent inhibitor elevated from 7 to 21 with recent studies investigating the usage of VYXEOS in extra individual populations (e.g., kids; type:clinical-trial,attrs:text message:NCT03826992″,term_id:NCT03826992″NCT03826992) and leukemias (e.g., lymphoblastic leukemias; … Continue reading Nanoparticle drug delivery systems have already been found in the clinic. ...

Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.

Get an answer for Two hypothetical ionic compounds are discovered with the chemical formulas XCl2 and YCl2, where X and Y represent symbols of the imaginary elements. Chemical analysis of the two compounds reveals that 0.25 mol XCl2 has a mass of 100.0 g and 0.50 mol YCl2has a mass of 125.0 g. a. What are the molar masses of XCl2 and YCl2? and find homework help for other Science questions at eNotes

Looking for online definition of dual-specificity phosphatase 12 in the Medical Dictionary? dual-specificity phosphatase 12 explanation free. What is dual-specificity phosphatase 12? Meaning of dual-specificity phosphatase 12 medical term. What does dual-specificity phosphatase 12 mean?

Abstract. Dual specificity phosphatases (DUSPs) constitute a heterogeneous group of protein tyrosine phosphatases with the ability to dephosphorylate Ser/Thr and Tyr residues from proteins, as well as from other non-proteinaceous substrates including signaling lipids. DUSPs include, among others, MAP kinase (MAPK) phosphatases (MKPs) and small-size atypical DUSPs. MKPs are enzymes specialized in regulating the activity and subcellular location of MAPKs, whereas the function of small-size atypical DUSPs seems to be more diverse. DUSPs have emerged as key players in the regulation of cell growth, differentiation, stress response, and apoptosis. DUSPs regulate essential physiological processes, including immunity, neurobiology and metabolic homeostasis, and have been implicated in tumorigenesis, pathological inflammation and metabolic disorders. Accordingly, alterations in the expression or function of MKPs and small-size atypical DUSPs have consequences essential to human disease, making these ...

The Laforin-Like Dual-Specificity Phosphatase SEX4 from Arabidopsis Hydrolyzes Both C6- and C3-Phosphate Esters Introduced by Starch-Related Dikinases and Thereby Affects Phase Transition of - ...

Looking for online definition of dual-specificity phosphatase MKP-5 in the Medical Dictionary? dual-specificity phosphatase MKP-5 explanation free. What is dual-specificity phosphatase MKP-5? Meaning of dual-specificity phosphatase MKP-5 medical term. What does dual-specificity phosphatase MKP-5 mean?

We have previously demonstrated that mitogen-activated protein kinase phosphatase 1, Mkp1, is expressed in the developing and rat adult substantia nigra and striatum, where it promotes the growth of nigral dopaminergic neurons. Mkp1 may therefore have therapeutic potential for Parkinsons disease. In the present study, we have assessed the expression of Mkp1 and TH in the substantia nigra and striatum of parkinsonian rat models. Expression was measured at 4 and 10 days post-lesion in the 6-hydroxydopamine (6-OHDA) medial forebrain bundle lesion model and after 4, 10 and 28 days in the 6-OHDA striatal lesion model. Our results show that Mkp1 expression was transiently up-regulated in the substantia nigra at 4 days post-6-OHDA administration in the two models while TH expression was decreased at the later time-points examined. These data suggest that Mkp1 may play a role in counteracting the neurotoxic effects of 6-OHDA in nigral dopaminergic neurons.

Sustained activation of extracellular signal-regulated kinase (ERK) has been detected previously in numerous tumors in the absence of RAS-activating mutations. However, the molecular mechanisms responsible for ERK-unrestrained activity independent of RAS mutations remain unknown. Here, we evaluated the effects of the functional interactions of ERK proteins with dual-specificity phosphatase 1 (DUSP1), a specific inhibitor of ERK, and S-phase kinase-associated protein 2 (SKP2)/CDC28 protein kinase 1b (CKS1) ubiquitin ligase complex in human hepatocellular carcinoma (HCC). Levels of DUSP1, as assessed by real-time reverse transcription-PCR and Western blot analysis, were significantly higher in tumors with better prognosis (as defined by the length of patients survival) when compared with both normal and nontumorous surrounding livers, whereas DUSP1 protein expression sharply declined in all HCC with poorer prognosis. In the latter HCC subtype, DUSP1 inactivation was due to either ...

A molecular volume control may one day be used to manipulate enzyme activity in order control the development and treatment of cancer, according to research at the Universities of Dundee and Bath.. The researchers have uncovered new functions of an enzyme called Dual-specificity phosphatase 5 (DUSP5), which will help scientists to better understand how tumours develop.. DUSP5 is known to switch off the activity of another enzyme, called ERK, which controls cell growth in a number of cancers, including colon, lung and melanoma. This would suggest that DUSP5 is a tumour suppressor, but studies have also shown that increased DUSP5 activity is observed in several human cancers.. Using cell-based models, the Dundee-Bath team have shown that the loss of DUSP5 can completely stop cancer cell formation by driving ERK activation to such high levels that it engages a natural protective mechanism within cells that makes them shut down. An analogy can be made to listening to the radio and being unable to ...

Styx & Don Felder: Renegades in the Fast Lane is a stage production with an exclusive set list. Styx with Tommy Shaw, James JY Young, Lawrence Gowan, Todd Sucherman and Ricky Phillips, plus an occasional surprise appearance by original bassist Chuck Panozzo, is joined by Don Felder-formerly of the Eagles. The show pays tribute to their 45 plus years of rock bands and most illustrious guitar legends.

The Styx series born from Of Orcs and Men is looking to be a much better success than its predecessor. Here is our Styx Shards of Darkness review.

Complete information for XCL1 gene (Protein Coding), X-C Motif Chemokine Ligand 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

ID: http://www.ncbi.nlm.nih.gov/gene/1196 Type: http://bio2vec.net/ontology/gene Label: CLK2 Synonyms: CLK2, CDC like kinase 2, dual specificity protein kinase CLK2, CLK kinase Alternative IDs: als API: GO SPARQL: GO ...

TY - JOUR. T1 - Functional involvement of Dual Specificity Phosphatase 16 (DUSP16), a c-Jun N-terminal kinase-specific phosphatase, in the regulation of T helper cell differentiation. AU - Musikacharoen, Tipayaratn. AU - Bandow, Kenjiro. AU - Kakimoto, Kyoko. AU - Kusuyama, Joji. AU - Onishi, Tomokazu. AU - Yoshikai, Yasunobu. AU - Matsuguchi, Tetsuya. PY - 2011/7/15. Y1 - 2011/7/15. N2 - Naïve CD4 +Thelper (Th) cells differentiate into distinct subsets of effector cells (Th1, Th2, Th17, and induced regulatory T cells (iTreg)) expressing different sets of cytokines upon encounter with presented foreign antigens. It has been well established that Th1/Th2 balance is critical for the nature of the following immune responses. Previous reports have demonstrated important roles of c-Jun N-terminal kinase (JNK) in Th1/Th2 balance, whereas the regulatory mechanisms of JNK activity in Th cells have not been elucidated. Here, we show that dual specificity phosphatase 16 (DUSP16, also referred to as MKP-M ...

Dual specificity phosphatase DUSP1 (otherwise known as mitogen-activated phosphatase 1 or MKP-1) dephosphorylates MAPKs, particularly p38, and negatively regulates innate immunity. Recent studies have shown that the DUSP1 gene is transcriptionally up-regulated by glucocorticoids (GCs) and that the antiinflammatory action of GCs is impaired in DUSP1-/- mice. Here we show that GC-mediated dephosphorylation of ERK-1 and ERK-2 activated by IgE receptor cross-linking is unimpaired in bone marrow-derived mast cells (BMMCs) of DUSP1-/- mice. Dephosphorylation of phospho-p38 MAPK is impaired but only at early times of GC treatment. Proinflammatory cytokine and chemokine gene expression (CCL2, IL-6, TNFalpha) is still down-regulated by GCs in BMMCs from DUSP1-/- mice, suggesting a compensatory mechanism for the GC action in these mice. In both DUSP1+/+ and DUSP1-/- BMMCs, GC up-regulated the expression of several phosphatase genes (DUSP2, DUSP4, DUSP9, and PEST domain-enriched tyrosine phosphatase). DUSP1-/-

The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...

Lead discovery kinases & phosphatases groups are post-translational modifications that regulate many disease states, including cancer, neurodegenerative diseases, diabetes, pain, autoimmunity, and cardiovascular diseases.

DUSP15 - DUSP15 (untagged)-Human dual specificity phosphatase 15 (DUSP15), transcript variant 3 available for purchase from OriGene - Your Gene Company.

DUSP3 - DUSP3 (untagged)-ORIGENE UNIQUE VARIANT 1 of Human dual specificity phosphatase 3 (DUSP3) available for purchase from OriGene - Your Gene Company.

PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Complete information for DUSP10 gene (Protein Coding), Dual Specificity Phosphatase 10, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

DUSP7 antibody [C1C3] (dual specificity phosphatase 7) for ICC/IF, IHC-P, WB. Anti-DUSP7 pAb (GTX109289) is tested in Human samples. 100% Ab-Assurance.

DUSP23 antibody [C1C3] (dual specificity phosphatase 23) for IHC-P, WB. Anti-DUSP23 pAb (GTX108245) is tested in Human, Mouse samples. 100% Ab-Assurance.

Thats the thing about stab-happy goblins: you can never be sure quite when theyll pop up. Styx was meant to continue his merry little adventures in Styx:

XCL1 protein is expressed in E. coli, processed, refolded and purified to yield the native, secreted form of the mature chemokine. XCL1 is a ligand for the G protein coupled receptor XCR1 with and EC50 ~ 50 nM. It has been shown the WT XCL1 is able to int

I have been coming here and to the Australian board daily to see if Donna had posted. Many will remember Gabby had surgery and had a possible rare, allergic reaction and suffered some paralysis. I just received this email from Donna: Hi Jen, Just a quick note as I never seem to have much time lately. Every day seems a little better. It has been 100 times worse than ever imagined. But she is definitely on the improve. She Is totally off all pain meds. May ask for occasional

Anti-inflammatory effects of glucocorticoids (GCs) are partly mediated by up-regulation of DUSP1 (dual specificity phosphatase 1), which dephosphorylates and inactivates mitogen-activated protein kinases. We identified putative GC-responsive regions containing GC receptor (GR) binding site consensus sequences that are well conserved between human and mouse DUSP1 loci in position, orientation, and sequence (at least 11 of 15 positions identical) and lie within regions of extended sequence conservation (minimum 65% identity over at least 100 bp). These were located approximately 29, 28, 24, 4.6, and 1.3 kb upstream of the DUSP1 transcription start site. The homology-based approach successfully identified four cis-acting regions that mediated transcriptional responses to dexamethasone. However, there was surprising interspecies divergence in site usage. This could not be explained by variations of the GR binding sites themselves. Instead, variations in flanking sequences appear to have driven the

Members of the MAPK phosphatase (MKP) protein family play critical roles in immune responses through differential regulation of MAPK activation. In this study, we show that MKP7, also known as dual-specificity phosphatase 16, was required for CD4+ T cell responses in vivo. Mkp7−/− CD4+ T cells exhibited enhanced ERK and JNK activation, and produced increased amount of IL-2 compared with Mkp7+/+ cells upon activation. Mkp7−/− CD4+ T cells were selectively defective in Th17 differentiation in vitro, which was rescued by blocking IL-2 or inhibition of ERK activation. Furthermore, mice carrying Mkp7−/− T cells were deficient in generation of Th17 and T follicular helper cells in vivo, and were resistant to autoimmune experimental encephalomyelitis. Our results thus demonstrate an essential role of MKP7 in effector T cell function. ...

This study uncovered a function of the dual specificity ERK MAP kinase phosphatase, MKP3, for the specification of mesenchymal progenitors in the somite sclerotome. We showed that Mkp3 was expressed in a twin-striped pattern, which closely matched the emergence of scleraxis transcripts along the anteroposterior somite edges (Fig. 1). This pattern suggested a link between the modulation of FGF signalling by MKP3 and scleraxis expression. We demonstrated that somitic expression of Mkp3 in the dorsal sclerotome was itself dependent on active ERK MAP kinase. This implied that FGF signalling in dorsal sclerotome cells is modulated by a negative feedback loop, which involves MKP3 and ERK MAP kinase. Indeed, we found that the levels of Mkp3 transcripts detected in response to FGF beads can cycle between extensive overexpression after a short exposure to complete loss of endogenous Mkp3 message after 24 hours (Fig. 3A-C; data not shown). We showed by western blot analysis that this dynamic response ...

Including the Sdp1 dual specificity phosphatase, which was demonstrated to negatively regulate Slt2 in the present study, four phosphatases have been identified as regulators of Slt2.. Treatment of cells with Congo red did not modify the binding of any of these proteins with Slt2, suggesting that phosphorylation is not regulating their interaction with this MAPK. Annotation program. Since expression of Sdp1 can reverse growth defects associated with hyperactivation of the Slt2 pathway and Slt2 is activated by phosphorylation, we investigated the possibility that phosphorylated Slt2 might be a direct target for the action of the Sdp1 putative phosphatase.. Second, a potent inhibitor of the as-kinase must be identified These additional observations verify that it is phosphorylation of Avo2 that makes a major contribution to interfering with TORC2 function ...

1KO7: Structure of the full-length HPr kinase/phosphatase from Staphylococcus xylosus at 1.95 A resolution: Mimicking the product/substrate of the phospho transfer reactions.

1KO7: Structure of the full-length HPr kinase/phosphatase from Staphylococcus xylosus at 1.95 A resolution: Mimicking the product/substrate of the phospho transfer reactions.

Styx returns in a new stealth adventure! Hired for a critical mission, explore and master huge open environments as Styx, alone or in coop with a friend. Assassinate or sneak past enemies - Humans, Elves and Dwarfs - but also much more fearsome, colossal creatures, and experiment with the new array of lethal abilities and weapons in your goblin assassins arsenal.

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XCL1 / Lymphotactin Protein LS-G5664 is a Recombinant Mouse XCL1 / Lymphotactin aa 22-114 produced in E. coli. It is biologically active.

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MODERATOR RIGHTS AND RESPONSIBILITIES: Head Moderator: @StyxChristi (STYXs Moderator) is the head of all moderation and represents STYX in correspondence to the fans as well as manages the website. The Head Moderator has the right to suspend or ban any member at any time or for any reason in accordance with these rule