A5050943814- Sphingolipid Metabolism and Signaling
- Cellular transport and secretion
- Receptor Mechanisms and Signaling
- Immune cells in cancer
- Caveolin-1 and cellular processes
- Adipose Tissue and Metabolism
- Cholesterol and Lipid Metabolism
- Lipid Membrane Structure and Behavior
- Lipid metabolism and biosynthesis
- Ion Transport and Channel Regulation
- Inflammasome and immune disorders
- Cell Adhesion Molecules Research
- Protein Kinase Regulation and GTPase Signaling
- Genomics and Chromatin Dynamics
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- RNA regulation and disease
- Fibroblast Growth Factor Research
- RNA Research and Splicing
- Immune Response and Inflammation
- Protein Tyrosine Phosphatases
- Eicosanoids and Hypertension Pharmacology
- Pancreatic function and diabetes
- Cardiovascular Disease and Adiposity
- Platelet Disorders and Treatments
- Nitric Oxide and Endothelin Effects
The Barbara Ann Karmanos Cancer Institute
2013-2016
Wayne State University
2013-2016
Active Biotech (Sweden)
2013
University of Louisville
2006-2008
University of Louisville Hospital
2008
UConn Health
1998-2003
University of Connecticut
1998-2001
Georgetown University
1998
Georgetown University Medical Center
1998
American Red Cross
1996
The sphingolipid metabolite sphingosine-1–phosphate (SPP) has been implicated as a second messenger in cell proliferation and survival. However, many of its biological effects are due to binding unidentified receptors on the surface. SPP activated heterotrimeric guanine nucleotide protein (G protein)–coupled orphan receptor EDG-1, originally cloned Endothelial Differentiation Gene – 1 . EDG-1 bound with high affinity (dissociation constant = 8.1 nM) specificity. Overexpression induced...
Sphingosine-1-phosphate (SPP), a bioactive lipid, acts both intracellularly and extracellularly to cause pleiotropic biological responses. Recently, we identified SPP as ligand for the G protein–coupled receptor Edg-1 (Lee, M.-J., J.R. Van Brocklyn, S. Thangada, C.H. Liu, A.R. Hand, R. Menzeleev, Spiegel, T. Hla. 1998. Science. 279:1552–1555). binds with remarkable specificity only sphinganine-1-phosphate displaced radiolabeled SPP, while other sphingolipids did not. Binding of resulted in...
Sphingosine 1-phosphate (SPP) binds to members of the endothelial differentiation gene family (EDG) receptors and leads diverse signaling events including cell survival, growth, migration differentiation. However, mechanisms how SPP activates these proangiogenic pathways are poorly understood. Here we show that signals through EDG-1 receptor heterotrimeric G protein Gi, leading activation serine/threonine kinase Akt phosphorylation substrate, nitric-oxide synthase (eNOS). Inhibition...
The edg-1 gene encodes an inducible G protein-coupled receptor (GPR) homologue that is induced during the in vitro differentiation of human endothelial cells. aim this study was to investigate protein-coupling and -signaling properties polypeptide. third cytosolic loop (i3) associates with Giα Goα polypeptides a guanosine 5′-O-(thiotriphosphate)-sensitive manner. Immunoprecipitation polypeptide transfected cells results co-precipitation Giα1 Giα3 polypeptides. These data strongly suggest...
EDG-1, an inducible G-protein-coupled receptor from vascular endothelial cells, is a high affinity for sphingosine 1-phosphate (SPP) (Lee, M-J., van Brocklyn, J. R., Thangada, S., Liu, C. H., Hand, A. Menzeleev, Spiegel, and Hla, T. (1998) Science 279, 1552–1555). In this study, we show that lysophosphatidic acid (LPA), platelet-derived bioactive lipid structurally related to SPP, agonist EDG-1. LPA binds EDG-1 with apparentKd of 2.3 μm. addition, binding induces phosphorylation,...
Sphingosine-1-phosphate (S1P) regulates various molecular and cellular events in cultured endothelial cells, such as cytoskeletal restructuring, cell-extracellular matrix interactions, intercellular junction interactions. We utilized the venular leakage model of cremaster muscle vascular bed Sprague-Dawley rats to investigate role S1P signaling regulation microvascular permeability. is mediated by family G protein-coupled receptors (S1P 1-5 receptors). 1 2 receptors, which transduce...
Abstract IFN-β production is a critical step in human innate immune responses and primarily controlled at the transcription level by highly ordered mechanisms. can be induced pattern-recognition receptors such as TLR4. S1P1 G protein-coupled receptor, which has high affinity for sphingosine 1-phosphate (S1P). Although many of signaling pathways leading to expression have been identified characterized, it still unclear how regulated primary gingival epithelial cells (HGECs). In this study, we...
Inflammation-induced vascular endothelial dysfunction can allow plasma proteins to cross the wall, causing edema. Proteins may traverse wall through two main pathways, paracellular and transcellular transport pathways. Paracellular involves changes in cell junction proteins, while caveolar transcytosis. Since both processes are associated with filamentous actin formation, pathways interconnected. Therefore, it is difficult differentiate prevailing role of one or other pathway during various...
Sphingosine-1-phosphate (S1P) receptor subtype 1 (S1P(1)), a G-protein coupled (GPCR), regulates many biological activities of endothelial cells (ECs). In this report, we show that S1P(1) receptors are present in the nuclei ECs by using various biochemical and microscopic techniques such as cellular fractionation, immunogold labeling, confocal analysis. Live cell imaging showed plasma membrane rapidly internalized subsequently translocated to nuclear compartment upon S1P stimulation....