- Receptor Mechanisms and Signaling
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Neuropeptides and Animal Physiology
- Protein Kinase Regulation and GTPase Signaling
- Galectins and Cancer Biology
- Neuroscience and Neuropharmacology Research
- RNA regulation and disease
- Celiac Disease Research and Management
- Pancreatic function and diabetes
- Neuroblastoma Research and Treatments
- Retinal Development and Disorders
- Toxin Mechanisms and Immunotoxins
- Cell Adhesion Molecules Research
- Ion channel regulation and function
- Calcium signaling and nucleotide metabolism
- Pancreatic and Hepatic Oncology Research
- Microscopic Colitis
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Lipid Membrane Structure and Behavior
- Protein Tyrosine Phosphatases
- Prion Diseases and Protein Misfolding
- Immunodeficiency and Autoimmune Disorders
- Heat shock proteins research
University of Chieti-Pescara
2016-2025
University of Turin
2023
University of Trento
2023
University of Milan
2023
University of Brescia
2023
Tecnologie Avanzate (Italy)
2020
Mario Negri Institute for Pharmacological Research
1993-2018
Mario Negri Sud Foundation
2006-2016
Mayo Clinic
2010
Istituto Neurologico Mediterraneo
2000-2001
G-protein-coupled receptor kinases (GRKs) are involved in the regulation of many receptors. As opposed to other GRKs, such as rhodopsin kinase (GRK1) or beta-adrenergic (beta ARK, GRK2), no substrate for GRK4 has been so far identified. Here we show that is expressed cerebellar Purkinje cells, where it regulates mGlu(1) metabotropic glutamate receptors, indicated by following: 1) When coexpressed heterologous cells (HEK293), signaling was desensitized an agonist-dependent manner (homologous...
Receptor phosphorylation is a key step in the process of desensitization beta-adrenergic and other related receptors. A selective kinase (called receptor kinase, beta ARK) has been identified which phosphorylates agonist-occupied form receptor. Recently bovine ARK cDNA cloned highest levels specific mRNA were found highly innervated tissues. It was proposed that may be primarily active on synaptic In present study, human sequenced. The sequence very similar to (the overall amino acid...
The size and integrity of the Golgi apparatus is maintained via a tightly controlled regulation membrane traffic using variety different signaling cytoskeletal proteins. We have recently observed that activation c-Src has profound effects on structure, leading to dramatically vesiculated cisternae in cell types. As large GTPase dynamin (Dyn2) been implicated vesiculation during secretion, we tested whether inhibiting Dyn2 activity by expression Dyn2K44A mutant or siRNA knockdown could...
Breast cancer is one of the most frequent human malignacies, and it therefore fundamental to identify underlying molecular mechanisms leading transformation. Among other causative agents in development breast cancers, an important role for reactive oxygen species (ROS) has emerged. However, studies on ROS have not reached specific conclusions, many issues remain controversial. In present study, we show that methionine sulfoxide reductase A (MsrA), which known protect proteins from oxidation...
The mechanism of transport through the Golgi complex is not completely understood, insofar as no single appears to account for all observations. Here, we compare soluble secretory proteins (albumin and α1-antitrypsin) with that supramolecular cargoes (e.g., procollagen) are proposed traverse by compartment progression–maturation. We show these much faster than procollagen while moving same stack. Moreover, present kinetic morphological observations indicate albumin occurs diffusion via...
Frizzled receptors mediate Wnt ligand signalling, which is crucially involved in regulating tissue development and differentiation, often deregulated cancer. In this study, we found that the gene encoding receptor frizzled 6 (FZD6) frequently amplified breast cancer, with an increased incidence triple-negative cancer (TNBC) subtype. Ablation of FZD6 expression mammary cell lines: (1) inhibited motility invasion; (2) induced a more symmetrical shape organoid three-dimensional cultures; (3)...
In this study, we investigated the regulation of different G protein-coupled receptor (GPCR)-stimulated signaling pathways by GPCR kinase 2 (GRK2). We used thyrotropin receptor, which is coupled to proteins, investigate Gαs- and Gαq-mediated (assessed cAMP inositol phosphate production, respectively). transfected cells, both were desensitized GRK2. However a kinase-dead GRK2 mutant (GRK2-K220R) only decreased indicating that could regulate Gαq through phosphorylation-independent mechanism....
Two Alternatively Spliced Forms of 0-Arrestin-1 and Arrestin expression function (5, 11).In these cells, we found that mRNA kinase activity PARK-1 a n d PARK-
Beta-adrenergic receptor kinase (beta ARK) is a serine-threonine involved in the process of homologous desensitization G-coupled receptors. beta ARK member multigene family, consisting six known subtypes, also named G protein-coupled kinases (GRK 1-6). In this study we investigated expression GRKs during T cell activation, which fundamental importance regulating immune responses. activation was induced by exposing mononuclear leukocytes (MNL) to PHA and confirmed tritiated thymidine...
The organization of intra-Golgi trafficking and the nature transport intermediates involved (e.g., vesicles, tubules, or tubular continuities) remain incompletely understood. It was recently shown that successive cisternae in Golgi stack are interconnected by membrane tubules form during arrival carriers from endoplasmic reticulum. Here, we examine mechanisms generation function these tubules. In principle, tubule formation might depend on several protein- and/or lipid-based mechanisms....
KDEL receptors (KDELRs) prevent the secretion of soluble chaperones and enzymes meant to reside in endoplasmic reticulum. While a single KDELR exists yeast (ERD2), three variants are present mammals, displaying high sequence similarity (73-83%). However, phylogenetic conservation differences diverse tissue distribution KDELRs suggest functional specialization. Here we show that, while all can KDEL-bearing clients, KDELR1 KDELR3 regulate production AGR2, key assistant mucin folding, opposite...
The involvement of mitogen-activated protein (MAP) kinases in the mitogenic effect thyrotropin (TSH) is not fully elucidated. In FRTL-5 cells, we found that MAP kinase (MEK) inhibitors UO126 and PD98059 substantially decreased TSH-induced DNA synthesis, indicating are involved TSH-stimulated proliferative response. Accordingly, TSH, forskolin (FSK) 8-bromo-cAMP induced a rapid (3 min) transient activation ERK1/2, as assessed by phosphorylation myelin basic ERK1/2. This was cAMP-dependent A...
G protein-coupled receptor kinase 4 (GRK4) presents some peculiar characteristics that make it a unique member within the GRK multigene family. For example, this is only for which four splice variants (GRK4α, −β, −γ, −δ) have been identified. We developed simple assay to study activity, and we found GRK4α, but not GRK4β, −δ, was able phosphorylate rhodopsin in an agonist-dependent manner. GRK4α activity inhibited by Ca<sup>2+</sup>/calmodulin (CaM) (IC<sub>50</sub> = 80 nM), direct...