Search results for "GTP-Binding Proteins"

Correlation between IgA tissue transglutaminase antibody ratio and histological finding in celiac disease.

2011

OBJECTIVES: Positivity of both immunoglobulin A anti-tissue transglutaminase (TTG) and anti-endomysium antibodies (EMA) has a positive predictive value of nearly 100% for celiac disease (CD). The objective of the present study was to evaluate whether patients of any age, with high pretest probability of CD and high titre of anti-TTG and EMA positivity, have a high probability of intestinal damage and may not require the biopsy for final diagnosis. METHODS: A retrospective analysis of 412 consecutively referred patients, age range 10 months to 72 years, who underwent small-bowel biopsy for suspicion of CD and positivity to both anti-TTG and EMA, was performed at 4 Italian centers. Biopsies w…

Calcium-Dependent Assembly of Centrin-G-Protein Complex in Photoreceptor Cells

2002

Photoexcitation of rhodopsin activates a heterotrimeric G-protein cascade leading to cyclic GMP hydrolysis in vertebrate photoreceptors. Light-induced exchanges of the visual G-protein transducin between the outer and inner segment of rod photoreceptors occur through the narrow connecting cilium. Here we demonstrate that transducin colocalizes with the Ca(2+)-binding protein centrin 1 in a specific domain of this cilium. Coimmunoprecipitation, centrifugation, centrin overlay, size exclusion chromatography, and kinetic light-scattering experiments indicate that Ca(2+)-activated centrin 1 binds with high affinity and specificity to transducin. The assembly of centrin-G-protein complex is medi…

Rho protein inhibition blocks protein kinase C translocation and activation.

1998

Small GTP-binding proteins of the Ras and Rho family participate in various important signalling pathways. Large clostridial cytotoxins inactivate GTPases by UDP-glucosylation. Using Clostridium difficile toxin B-10463 (TcdB) for inactivation of Rho proteins (RhoA/Rac/Cdc42) and Clostridium sordellii lethal toxin-1522 (TcsL) for inactivation of Ras-proteins (Ras/Rac/Ral, Rap) the role of these GTPases in protein kinase C (PKC) stimulation was studied. Phorbol-myristate-acetate (PMA) induced a rapid PKC translocation to and activation in the particulate cell fraction as determined by PKC-activity measurements and Western blots for PKC alpha. These effects were blocked by TcdB inhibiting Rho …

Tissue transglutaminase in HCV infection.

2003

Coupling of endothelin receptors to the ERK/MAP kinase pathway. Roles of palmitoylation and G(alpha)q.

2001

Endothelins are potent mitogens that stimulate extracellular signal-regulated kinases (ERK/MAP kinases) through their cognate G-protein-coupled receptors, ET(A) and ET(B). To address the role of post-translational ET receptor modifications such as acylation on ERK activation and to identify relevant downstream effectors coupling the ET receptor to the ERK signaling cascades we have constructed a panel of palmitoylation-deficient ET receptor mutants with differential G(alpha) protein binding capacity. Endothelin-1 stimulation of wild-type ET(A) or ET(B) induced a fivefold to sixfold increase in ERK in COS-7 and CHO cells whereas full-length nonpalmitoylated ET(A) and ET(B) mutants failed to …

Cloning of Rac and Rho-GDI from tobacco using an heterologous two-hybrid screen.

2000

International audience; To examine whether molecular similarities exist between the animal and plant Rho GTPase signaling pathways, we have developed a heterologous two-hybrid screening method. By this technique, we have cloned a cDNA encoding a tobacco Rac-like protein able to interact with a mammalian Rho-GDI. In a second screen this tobacco Rac was used as a bait and a tobacco homologue of Rho-GDI was identified. These results show that some components of the animal and plant Rac signaling pathways are similar enough to allow their interaction in an heterologous approach. Moreover these data suggest a similar regulation of Rho GTPases in animals and plants.

Genome-wide Association Studies Identify Genetic Loci Associated with Albuminuria in Diabetes

2016

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10−10). Gene-by-diabetes interactions were…

Phospholipase D in heart: basal activity and stimulation by phorbol esters and aluminum fluoride

1992

Evidence for a general role of phospholipase D in signal transduction is accumulating. In the present study, the activity of the enzyme was investigated in heart tissue under basal conditions and after addition of phorbol esters or aluminum fluoride (AlF inf4 sup− ; 10 mM NaF plus 10 μM AlCl3). Atria of rats and chickens were incubated with [3H]-myristic acid in order to label preferentially phosphatidylcholine. Under basal conditions, the tissues generated choline and phosphatidic acid (PtdOH), the primary catalytic products of phospholipase D. When 0.5 or 2.0% ethanol was present, [3H]-phosphatidyl-ethanol (PETH) was rapidly formed at the expense of [3H]-PtdOH. This transphosphatidylation…

Phospholipase D in rat myocardium: formation of lipid messengers and synergistic activation by G-protein and protein kinase C.

1998

Activation of phospholipase D (PLD) and phosphoinositide-specific phospholipase C (PI-PLC) by fluoride, to stimulate heterotrimeric G-proteins, and by phorbol esters, to stimulate protein kinase C (PKC), was studied in rat atria. Fluoride and 4beta-phorbol-12beta,13alpha-dibutyrate (PDB), in contrast to 4beta-phorbol-13alpha-acetate (PAc), activated PLD, catalyzing the formation of [3H]-phosphatidylethanol ([3H]-PETH), [3H]-phosphatidic acid ([3H]-PA), choline and sn-1,2-diacylglycerol (DAG). Basal PLD activity was resistant to drastic changes in Ca2+ and to Ro 31-8220, a PKC inhibitor, but was decreased by genistein, an inhibitor of tyrosine kinase, and increased by vanadate, a tyrosine ph…

Mechanisms of Ca2+ liberation at fertilization

2005

The mechanisms underlying the Ca2+ release at fertilization of several animal organisms are reported. Four main classical theories are described, i.e., that of Ca2+ release following simple sperm contact and a G protein stimulation; that of simple sperm contact followed by a tyrosine kinase receptor activation; that of the necessity of introduction by sperm into the egg of molecules for Ca2+ release; and that the molecule introduced into the marine eggs for Ca2+ release is the same Ca2+. Two other mechanisms for Ca2+ release are also illustrated: that of ryanodine receptor stimulation and that of NAADP formation.