A5042675661- Receptor Mechanisms and Signaling
- Cellular transport and secretion
- Protein Kinase Regulation and GTPase Signaling
- Ion channel regulation and function
- Renin-Angiotensin System Studies
- Electrolyte and hormonal disorders
- Pancreatic function and diabetes
- Ion Transport and Channel Regulation
- Neuroendocrine regulation and behavior
- Lipid Membrane Structure and Behavior
- Retinal Development and Disorders
- PI3K/AKT/mTOR signaling in cancer
- Calcium signaling and nucleotide metabolism
- Computational Drug Discovery Methods
- Hormonal Regulation and Hypertension
- bioluminescence and chemiluminescence research
- Neuropeptides and Animal Physiology
- Pharmacological Receptor Mechanisms and Effects
- Cell death mechanisms and regulation
- Adenosine and Purinergic Signaling
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- RNA regulation and disease
- Monoclonal and Polyclonal Antibodies Research
- Mass Spectrometry Techniques and Applications
- Melanoma and MAPK Pathways
Semmelweis University
2014-2024
Hungarian Research Network
2021-2024
Eötvös Loránd University
2021-2023
Research Network (United States)
2023
HUN-REN Research Centre for Natural Sciences
2023
Hungarian Academy of Sciences
2001-2021
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2001-2015
National Institutes of Health
2001-2015
Institute of Materials and Environmental Chemistry
2015
Molecular Oncology (United States)
2008
The membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P<sub>2</sub> or PIP<sub>2</sub>] regulates many ion channels. There are conflicting reports on the effect of PtdIns(4,5)P<sub>2</sub> transient receptor potential vanilloid 1 (TRPV1) We show that in excised patches and other phosphoinositides activate PIP<sub>2</sub> scavenger poly-Lys inhibits TRPV1. TRPV1 currents undergo desensitization exposure to high concentrations capsaicin presence extracellular...
The PH domains of OSBP and FAPP1 fused to GFP were used monitor PI(4)P distribution in COS-7 cells during manipulations PI 4-kinase (PI4K) activities. Both associated with the Golgi small cytoplasmic vesicles, a fraction OSBP-PH was found at plasma membrane (PM). Inhibition type-III PI4Ks 10 microM wortmannin (Wm) significantly reduced but did not abolish localization either domains. Downregulation PI4KIIalpha or PI4KIIIbeta by siRNA former case any remaining eliminated Wm treatment. PLC...
Phosphorylation of phosphatidylinositol (PI) to PI 4-phosphate is one the key reactions in production phosphoinositides, lipid regulators several cellular functions. This reaction catalyzed by multiple enzymes that belong either type II or III family 4-kinases. Type are structurally similar 3-kinases and sensitive 3-kinase inhibitors. In contrast, recent cloning first 4-kinase enzyme defined a novel family. Here we characterize new member this family, IIβ has been identified NCBI data base...
Type III phosphatidylinositol (PtdIns) 4-kinases (PI4Ks) have been previously shown to support plasma membrane phosphoinositide synthesis during phospholipase C activation and Ca(2+) signaling. Here, we use biochemical imaging tools monitor changes in the combination with pharmacological genetic approaches determine which of type PI4Ks (alpha or beta) is responsible for supplying phosphoinositides agonist-induced Using inhibitors that discriminate between alpha- beta-isoforms PI4Ks,...
Phosphatidylinositol 4-kinases (PI4K) catalyze the first step in synthesis of phosphatidylinositol 4,5-bisphosphate, an important lipid regulator several cellular functions. Here we show that Ca2+-binding protein, neuronal calcium sensor-1 (NCS-1), can physically associate with type III PI4Kβ functional consequences affecting kinase. Recombinant PI4Kβ, but not its glutathioneS-transferase-fused form, showed enhanced PI kinase activity when incubated recombinant NCS-1, only if latter was...
The recently identified ceramide transfer protein, CERT, is responsible for the bulk of transport from endoplasmic reticulum (ER) to Golgi. CERT has a C-terminal START domain binding and an N-terminal pleck-strin homology that binds phosphatidylinositol 4-phosphate suggesting (PI) 4-kinases are involved in regulation CERT-mediated transport. In present study fluorescent analogues were used follow ER Golgi determine which four mammalian PI this process. Overexpression pleckstrin domains bind...
Abstract Background Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5) P 2 ] is a critically important regulatory phospholipid found in the plasma membrane of all eukaryotic cells. In addition to being precursor second messengers, PtdIns(4,5) also regulates ion channels and transporters serves endocytic machinery by recruiting clathrin adaptor proteins. Visualization localization dynamic changes levels living cells critical understanding biology . This has been mostly achieved with use...
Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a recently discovered rare disease caused by gain-of-function mutations the V2 vasopressin receptor gene, AVPR2. To date, Phe229 and Arg137 have been identified as in (V2R). These lead to hyponatremia, which may clinical symptoms infants. Here we present newly I130N substitution exon 2 V2R gene family, causing NSIAD. This mutation resulted constitutive activity with cyclic adenosine monophosphate (cAMP) generation HEK293 cells....
β-Arrestins are key regulators and signal transducers of G protein-coupled receptors (GPCRs). The interaction between β-arrestins is generally believed to require both receptor activity phosphorylation by GPCR kinases. In this study, we investigated whether able bind second messenger kinase-phosphorylated, but inactive as well. Because heterologous a common phenomenon among GPCRs, mode β-arrestin activation may represent novel mechanism transduction cross-talk. Here demonstrate that protein...
The minimum structure of the Raf-1 serine/threonine kinase that recognizes active Ras was used to create a green fluorescent fusion protein (GFP) for monitoring activation in live cells. In spite its ability bind activated vitro, binding domain (RBD) (Raf-1[51-131]GFP) failed detect Ras-transformed NIH 3T3 fibroblasts and required addition cysteine-rich (CRD) (Raf-1[51-220]GFP) show clear localization plasma membrane ruffles. normal cells, showed minimal enhanced after stimulation with...
Receptor endocytosis plays an important role in regulating the responsiveness of cells to specific ligands. Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] has been shown be crucial for some cell surface receptors, such as EGF and transferrin but its G-protein-coupled receptor internalization not investigated. By using luciferase-labeled type 1 angiotensin II (AT1R), 2C serotonin (5HT2CR) or β(2) adrenergic (β2AR) receptors fluorescently tagged proteins (β-arrestin-2,...
The stabilization of different active conformations G protein–coupled receptors is thought to underlie the varying efficacies biased and balanced agonists. Here, profiling activation signal transducers by angiotensin II type 1 receptor (AT R) agonists revealed that extent kinetics β-arrestin binding exhibited substantial ligand-dependent differences, which were lost when internalization was inhibited. When AT R endocytosis prevented, even weak partial pathway acted as full or near-full...
Biased agonism on the type I angiotensin receptor (AT<sub>1</sub>-R) can achieve different outcomes via activation of G protein–dependent and –independent cellular responses. In this study, we investigated whether biased AT<sub>1</sub>-R lead to regulation intracellular processing receptor. We analyzed <i>β</i>-arrestin binding, endocytosis, subsequent trafficking steps, such as early late phases recycling in human embryonic kidney 293 cells expressing wild-type or mutant receptors response...
Molecular modeling and site directed mutagenesis were used to analyze the structural features determining unique inhibitor sensitivities of type-III phosphatidylinositol 4-kinase enzymes (PI4Ks). Mutation a highly conserved Tyr residue that provides bottom hydrophobic pocket for ATP yielded PI4KIIIbeta enzyme showed greatly reduced wortmannin sensitivity was catalytically still active. Similar substitutions not tolerated in type-IIIalpha rendering it inactive. Two Cys residues located active...
The binding and function of β-arrestins are regulated by specific phosphorylation motifs present in G protein-coupled receptors (GPCRs). However, the exact arrangement phosphorylated amino acids responsible for establishing a stable interaction remains unclear. We employ 1D sequence convolution model trained on GPCRs with established β-arrestin-binding properties. With this approach, acid characteristic that form interactions can be identified, pattern we name "arreSTick." Intriguingly,...
Virtually all functions of a cell are influenced by cytoplasmic [Ca 2+ ] increases. Inositol 1,4,5-trisphosphate receptor (IP 3 R) channels, located in the endoplasmic reticulum (ER), release Ca response to binding second messenger, IP .IP Rs thus part information chain interpreting external signals and transforming them into transients. function as tetramers, each unit comprising an N-terminal ligand-binding domain (LBD) C-terminal channel linked long regulatory region. It is not yet...