A5072382215- Protein Tyrosine Phosphatases
- Galectins and Cancer Biology
- Cytokine Signaling Pathways and Interactions
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- Financial Distress and Bankruptcy Prediction
- Yersinia bacterium, plague, ectoparasites research
- Alkaline Phosphatase Research Studies
- Nitric Oxide and Endothelin Effects
- Enzyme Structure and Function
- Credit Risk and Financial Regulations
- Biochemical and Molecular Research
- Cell Adhesion Molecules Research
- Pharmacological Effects of Natural Compounds
- Immune Cell Function and Interaction
- Atherosclerosis and Cardiovascular Diseases
- ATP Synthase and ATPases Research
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Chromatography in Natural Products
- Finance, Taxation, and Governance
- Protein Kinase Regulation and GTPase Signaling
- Transplantation: Methods and Outcomes
- Brucella: diagnosis, epidemiology, treatment
Instituto de Biomedicina y Genética Molecular de Valladolid
2006-2024
Universidad de Valladolid
1997-2024
Bank of Spain
2019-2023
Ministerio de Educación Cultura y Deporte
2022
Consejo Superior de Investigaciones Científicas
1996-2020
Sanford Burnham Prebys Medical Discovery Institute
2000-2007
Cancer Research Center
2000-2004
Service de Santé des Armées
2003
The 21-kDa dual specific protein phosphatase VH1-related (VHR) is one of the smallest known phosphatases, and its function has remained obscure. We report that this enzyme expressed in lymphoid cells not induced by T cell antigen receptor like other specificity phosphatases. Introduction exogenous VHR into Jurkat caused a marked decrease transcriptional activation nuclear factor activated an activator protein-1-driven reporter gene response to ligation receptors. inhibition was...
In this paper we study the performance of several machine learning (ML) models for credit default prediction. We do so by using a unique and anonymized database from major Spanish bank. compare statistical simple traditionally used model like Logistic Regression (Logit), with more advanced ones Lasso penalized logistic regression, Classification And Tree (CART), Random Forest, XGBoost Deep Neural Networks. Following process deployed supervisory validation Internal Rating-Based (IRB) systems,...
New reports show that the fi nancial sector is increasingly adopting machine learning (ML) tools to manage credit risk. In this environment, supervisors face challenge of allowing institutions benefi t from technological progress and financial innovation, while at same ensuring compatibility with regulatory requirements neutrality observed. We propose a new framework for measure costs ts evaluating ML models, aiming shed more light on technology’s alignment regulation. follow three steps....
A key virulence factor for Yersinia pestis, the etiologic agent of plague, is tyrosine phosphatase YopH, which bacterium injects into host cells. We report that treatment human T lymphocytes with a recombinant membrane-permeable YopH resulted in severe reduction intracellular phosphorylation and inhibition cell activation. The primary signal transducer antigen receptor, Lck kinase, was specifically precipitated by substrate-trapping mutant, dephosphorylated at its positive regulatory site,...
A high protein tyrosine phosphatase (PTPase) activity is required to maintain circulating T lymphocytes in a resting phenotype, and limit the initiation of cell activation. We report that 15 currently known 24 intracellular PTPases are expressed cells, namely HePTP, TCPTP, SHP1, SHP2, PEP, PTP-PEST, PTP-MEG2, PTEN, PTPH1, PTP-MEG1, PTP36, PTP-BAS, LMPTP, PRL-1 OV-1. Most were found cytosol many enriched at plasma membrane. Only TCPTP PTP-MEG2 had subcellular localizations essentially...
Potassium channel tetramerization domain (KCTD) proteins contain a bric-a-brac, tramtrak and broad complex (BTB) that is most similar to the (T1) of voltage-gated potassium channels. Some BTB-domain-containing have been shown recently participate as substrate-specific adaptors in multimeric cullin E3 ligase reactions by recruiting for ubiquitination subsequent degradation proteasome. Twenty-two KCTD found human genome, but their functions are largely unknown. In this study, we characterized...
The ZAP-70 protein-tyrosine kinase plays a central role in signaling from the T cell antigen receptor. Recruitment and activation of are transient terminated by phosphorylation negative regulatory tyrosine residues dephosphorylation positively acting sites. We report that low molecular weight phosphatase (LMPTP) specifically dephosphorylates Tyr-292 ZAP-70, thereby counteracting inactivation ZAP-70. Expression levels LMPTP resulted increased phosphorylation, presumably at activating Tyr-493...
Yersinia are causative agents in human diseases ranging from gastrointestinal syndromes to Bubonic Plague. There is increasing risk of misuse infectious agents, such as pestis, weapons terror well instruments warfare for mass destruction. YopH an essential virulence factor whose protein-tyrosine phosphatase (PTP) activity required pathogenicity. Consequently, there considerable interest developing potent and selective inhibitors novel anti-plague agents. We have screened a library 720...
Abstract Inflammatory mediators derived from arachidonic acid (AA) alter the function of dendritic cells (DC), but data regarding their biosynthesis resulting stimulation opsonic and nonopsonic receptors are scarce. To address this issue, production eicosanoids by human monocyte-derived DC stimulated via involved in Ag recognition was assessed. Activation FcγR induced AA release, short-term, low-grade PG biosynthesis, IL-10 production, whereas zymosan, which contains ligands both mannose...
A cDNA encoding a novel, human, dual-specific protein phosphatase was identified in the Incyte data base. The open reading frame predicted of 184 amino acids related to the<i>Vaccinia</i> virus VH1 and human VH1-related (VHR) phosphatases. Expression VHR-related MKPX (VHX) highest thymus, but also detectable monocytes lymphocytes. VHX-specific antiserum detected with an apparent molecular mass 19 kDa many cells, including T lymphocytes monocytes. VHX expression not induced by cell...
Abstract Cytokine-induced tyrosine phosphorylation of the transcription factor STAT5 is required for its transcriptional activity. In this article we show that small dual-specificity phosphatase VHR selectively dephosphorylates IFN-α- and β-activated, tyrosine-phosphorylated STAT5, leading to subsequent inhibition function. Phosphorylation at Tyr138 was activity toward STAT5. addition, Src homology 2 domain effective dephosphorylation by VHR. The kinase Tyk2, which mediates also responsible Tyr138.
The effect of two derivatives salicylate, 2‐hydroxy‐4‐trifluoromethylbenzoic acid (HTB) and 2‐acetoxy‐4‐trifluoromethylbenzoic (triflusal), on the activation NF‐κB elicited by tumour necrosis factor‐α (TNF‐α) human umbilical vein endothelial cells (HUVEC) was tested. expression mRNA vascular cell adhesion molecule‐1 (VCAM‐1) studied as an example a gene which is regulated NF‐κB. To extend these findings to other systems, induction nitric oxide synthase in rat adherent peritoneal macrophages...
The cholinergic agonist carbachol induced the release of arachidonic acid in 1321N1 astrocytoma cell line, and this was blocked by atropine, suggesting involvement muscarinic receptors. To assess mechanisms signalling involved response to carbachol, a set compounds characterized eliciting responses through different tested. A combination 4β-phorbol 12β-myristate 13α-acetate thapsigargin, an inhibitor endomembrane Ca2+-ATPase that induces prolonged elevation cytosolic Ca2+ concentration,...
To avoid detection and targeting by the immune system, plague-causing bacterium Yersinia pestis uses a type III secretion system to deliver set of inhibitory proteins into cytoplasm cells. One these is an exceptionally active tyrosine phosphatase termed YopH, which paralyzes lymphocytes macrophages dephosphorylating critical kinases signal transduction molecules. Because Y. strains lacking YopH are avirulent, we out develop small molecule inhibitors for YopH. We used novel cost-effective...
YopH is an exceptionally active tyrosine phosphatase that essential for virulence of Yersinia pestis, the bacterium causing plague. breaks down signal transduction mechanisms in immune cells and inhibits response. Only a few substrates have been characterized so far, instance p130Cas Fyb, but view potency great number proteins involved signalling pathways it quite likely more are this phosphatase. In respect, we show here interaction with several not shown before, such as Gab1, Gab2, p85,...
Climate change and its management mitigation are unquestionably among the main risks facing our society in coming decades. The financial sector plays a key role this challenge, firstly because of exposure consequent capital shocks if risk crystallises, secondly it has task financing investments needed to transform economy into sustainable one. This article reviews various initiatives under way private introduce variable "sustainability" decision-making process order achieve balance sheet...