A5023862478- Cellular transport and secretion
- Protein Kinase Regulation and GTPase Signaling
- Lipid Membrane Structure and Behavior
- Pancreatic function and diabetes
- Erythrocyte Function and Pathophysiology
- Receptor Mechanisms and Signaling
- Calcium signaling and nucleotide metabolism
- Endoplasmic Reticulum Stress and Disease
- Lysosomal Storage Disorders Research
- Mast cells and histamine
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Adenosine and Purinergic Signaling
- Polyamine Metabolism and Applications
- Lipid metabolism and biosynthesis
- Trypanosoma species research and implications
- Ion channel regulation and function
- Biomedical Research and Pathophysiology
- Sphingolipid Metabolism and Signaling
- Peroxisome Proliferator-Activated Receptors
- Biotin and Related Studies
- Metabolism, Diabetes, and Cancer
- Phosphodiesterase function and regulation
- Blood disorders and treatments
- Retinal Development and Disorders
- Ubiquitin and proteasome pathways
University College London
2015-2024
UCL Australia
2002
University of London
1994-2001
University of Leicester
1998
Rockefeller University
1991-1998
Oxford Research Group
1994
Birkbeck, University of London
1994
University of Reading
1994
Inserm
1988
Hôpital Saint-Louis
1988
Activation of the phospholipase D (PLD) pathway is a widespread response when cells are activated by agonists that bind receptors on cell surface. A 16-kD cytosolic component can reconstitute guanosine triphosphate (GTP)-mediated activation in HL60 depleted their cytosol permeabilization. This factor was purified and identified as two small GTP-binding proteins, ARF1 ARF3. Recombinant substituted for ARF proteins reconstitution assay. These results indicate downstream effector The...
Sterol traffic between the endoplasmic reticulum (ER) and plasma membrane (PM) is a fundamental cellular process that occurs by poorly understood non-vesicular mechanism. We identified novel, evolutionarily diverse family of ER proteins with StART-like lipid transfer domains studied them in yeast. from Ysp2p its paralog Lam4p specifically bind sterols, Ysp2p, their homologs Ysp1p Sip3p target punctate ER-PM contact sites distinct those occupied known tethers. The activity reflected...
The concentration-dependence on exogenous ATP of activation and inhibition mast-cell histamine secretion, phosphatidylinositol labelling leakage metabolites shows that all these functions are regulated by the free acid ATP4-. Maximal secretion occur with ATP4- at approx. 2 microM, but higher concentrations, which cause labelling, required to maximize 32P-labelled metabolites. Both enhancement (due low high concentrations respectively) rapid in onset; is characterized a delay, especially...
Genetic and biochemical studies have shown that the phosphatidylinositol (PtdIns) 3-kinase encoded by yeast VPS34 gene is required for efficient sorting delivery of proteins to vacuole. A human homologue product has recently been characterized as part a complex with cellular protein 150 kDa (Volinia, S., Dhand, R., Vanhaesebroeck, B., MacDougall, L. K., Stein, Zvelebil, M. J., Domin, Panaretou, C., Waterfield, D. (1995) EMBO J. 14, 3339-3348). Here, cDNA cloning used show amino acid sequence...
Provision of GTP (or other nucleotides capable acting as ligands for activation G-proteins) together with Ca2+ (at micromolar concentrations) is both necessary and sufficient to stimulate exocytotic secretion from mast cells permeabilized streptolysin-O. its analogues, through their interactions Gp, also activate polyphosphoinositide-phosphodiesterase (PPI-pde generating inositol 1,4,5-trisphosphate diglyceride [DG]). We have used labeled [3H]inositol test whether the requirement in...
Rat mast cells, pretreated with metabolic inhibitors and permeabilized by streptolysin-O, secrete histamine when provided Ca2+ (buffered in the micromolar range) nucleoside triphosphates. We have surveyed ability of various exogenous nucleotides to support or inhibit secretion. The preferred rank order secretion is ITP greater than XTP GTP much ATP. Pyrimidine (UTP CTP) are without effect. Nucleoside diphosphates included alongside plus 2'-deoxyGDP GDP o-GDP ADP approximately equal...
Studies of inositol lipid-specific phospholipase C (PLC) have elucidated the main regulatory pathways for PLCβ and PLCγ but regulation PLCΔ isoenzymes still remains obscure. Here we demonstrate that an increase in Ca2+ ion concentration within physiological range (0.1-10 μM) is sufficient to stimulate PLCΔ1, not PLCγ1 PLCβ1, hydrolyse cellular lipids present permeabilized cells. The activity PLCΔ1 further enhanced presence phosphatidylinositol transfer protein (PI-TP). Both full activation...
1. The concentration dependence on ATP of mast cell histamine secretion in the presence various concentrations Mg2+ and Ca2+ confirms that agonist form is free (ATP(free) not bound to divalent cations, i.e. ATP4-. It induces 50% activation at about 1.2 microM, maximal 2.7 microM self-inhibition 4.4 microM. 2. cations were used buffer ATP(tree) range 1-8 much higher ATP(total). In addition its effect as a for ATP, required secretion. 3. With ATP(free) 1 time-course characterized by delay 10...
Despite its significance, the role of lipid metabolism in NLRP3 inflammasome remains elusive. Here, we reveal a critical for fatty acid synthase (FASN) activation. We demonstrate that pharmacological or genetic depletion FASN dampens activation primary mouse and human macrophages mice. This disruption is contingent upon activity. Accordingly, abolishing cellular palmitoylation, post-translational modification which product palmitate reversibly conjugated to cysteine residues target proteins,...
Stimulation of phosphatidylinositol-4,5-bisphosphate (PIP 2 ) hydrolysis is a widespread mechanism for receptor-mediated signaling in eukaryotes. Cytosolic phosphatidylinositol transfer protein (PITP) necessary guanosine triphosphate (GTP)-dependent PIP by phospholipase C-β (PLC-β), but the role PITP unclear. C-γ (PLC-γ) A431 human epidermoid carcinoma cells treated with epidermal growth factor (EGF) required PITP. PI-4 kinase EGF also Coprecipitation studies revealed an EGF-dependent...