A5026510433- Sphingolipid Metabolism and Signaling
- Drug Transport and Resistance Mechanisms
- Immune cells in cancer
- Erythrocyte Function and Pathophysiology
- Inflammasome and immune disorders
- Endoplasmic Reticulum Stress and Disease
- Lipid Membrane Structure and Behavior
- Fibroblast Growth Factor Research
- Cellular transport and secretion
- Cancer Mechanisms and Therapy
- Cholesterol and Lipid Metabolism
- Cancer, Hypoxia, and Metabolism
- Protein Kinase Regulation and GTPase Signaling
- Histone Deacetylase Inhibitors Research
- Enzyme function and inhibition
- PI3K/AKT/mTOR signaling in cancer
- Cell death mechanisms and regulation
- Epigenetics and DNA Methylation
- Cytokine Signaling Pathways and Interactions
- Mast cells and histamine
- Microtubule and mitosis dynamics
- RNA modifications and cancer
- Phagocytosis and Immune Regulation
- Psoriasis: Treatment and Pathogenesis
- Autophagy in Disease and Therapy
Roswell Park Comprehensive Cancer Center
2016-2024
Virginia Commonwealth University
2008-2018
Niigata University
2018
University at Buffalo, State University of New York
2018
Universidad Maimónides
2015
Virginia Commonwealth University Medical Center
2014
Children's Hospital of Richmond at VCU
2009-2013
Virginia Cancer Institute
2008
VCU Massey Comprehensive Cancer Center
2008
Bose Institute
1997-2004
Epigenetic Signals The lipid sphingosine-1-phosphate (S1P) is a signaling molecule that binds to receptors on the cell surface initiate biochemical changes control range of biological processes from growth and survival immune reactions. Hait et al. (p. 1254 ) report S1P can also function by direct binding nuclear enzymes, histone deacetylases (HDACs) 1 2. enzyme generates S1P, sphingosine kinase 2 (ShpK2) present in nucleus complexes with HDAC1 HDAC2. Generation its HDACs inhibited...
The potent sphingolipid metabolite sphingosine 1-phosphate is produced by phosphorylation of catalyzed kinase (SphK) types 1 and 2. In contrast to pro-survival SphK1, the putative BH3-only protein SphK2 inhibits cell growth enhances apoptosis. Here we show that catalytic activity also contributes its ability induce Overexpressed increased cytosolic free calcium induced serum starvation. Transfer mitochondria was required for SphK2-induced apoptosis, as death cytochrome c release abrogated...
The potent lipid mediator sphingosine-1-phosphate (S1P) regulates diverse physiological processes by binding to 5 specific GPCRs, although it also has intracellular targets. Here, we demonstrate that S1P, produced in the mitochondria mainly sphingosine kinase 2 (SphK2), binds with high affinity and specificity prohibitin (PHB2), a highly conserved protein mitochondrial assembly function. In contrast, S1P did not bind closely related PHB1, which forms large, multimeric complexes PHB2. from...
Sphingosine 1-phosphate (S1P), a potent sphingolipid mediator produced by sphingosine kinase isoenzymes (SphK1 and SphK2), regulates diverse cellular processes important for breast cancer progression acting in an autocrine and/or paracrine manner. Here we show that SphK1, but not SphK2, increased S1P export from MCF-7 cells. Whereas both estradiol (E2) epidermal growth factor-activated SphK1 production of S1P, only E2 stimulated rapid release dihydro-S1P E2-induced required estrogen...
Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis these connections remain poorly understood. Here, we show that in patients animal models, sufficient cause increased expression of bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), which mediates pathogenesis. A high-fat diet was to upregulate sphingosine kinase 1 (SphK1), enzyme produces S1P, along its receptor S1PR1 syngeneic...
Sphingosine‐1‐phosphate (S1P) is a potent lysolipid involved in variety of biological responses important for cancer progression. Therefore, we investigated the role sphingosine kinase type 1 (SphK1), enzyme that makes S1P, motility, growth, and chemoresistance MCF‐7 breast cells. Epidermal growth factor (EGF), an progression, activated translocated SphK1 to plasma membrane. was required EGF‐directed motility. Downregulation cells reduced EGF‐ serum‐stimulated enhanced sensitivity...
l-myo-Inositol-1-phosphate synthase (EC 5.5.1.4, MIPS), an evolutionarily conserved enzyme protein, catalyzes the synthesis of inositol, which is implicated in a number metabolic reactions biological kingdom. Here we report on isolation gene (PINO1) for novel salt-tolerant MIPS from wild halophytic rice, Porteresia coarctata (Roxb.) Tateoka. Identity PINO1 was confirmed by functional complementation yeast inositol auxotrophic strain. Comparison nucleotide and deduced amino acid sequences...
Bile acids are important hormones during the feed/fast cycle, allowing liver to coordinately regulate nutrient metabolism. How they accomplish this has not been fully elucidated. Conjugated bile activate both ERK1/2 and AKT signaling pathways via sphingosine 1-phosphate receptor 2 (S1PR2) in rodent hepatocytes vivo. Here, we report that feeding mice a high-fat diet, infusion of taurocholate into chronic fistula rat, or overexpression gene encoding S1PR2 mouse significantly upregulated...
Abstract Sphingosine-1-phosphate is a potent sphingolipid mediator of diverse processes important for brain tumors, including cell growth, survival, migration, invasion, and angiogenesis. Sphingosine kinase 1 (SphK1), one the two isoenzymes that produce sphingosine-1-phosphate, up-regulated in glioblastoma has been linked to poor prognosis patients with multiforme (GBM). In present study, we found isotype-specific SphK1 inhibitor, SK1-I, suppressed growth LN229 U373 lines nonestablished...
Sphingosine 1-phosphate (S1P), a potent lipid mediator, is ligand for family of five G protein-coupled receptors (S1P(1-5)) that have been shown to regulate variety biological responses important cancer progression. The cellular level S1P low and tightly regulated in spatio-temporal manner through its synthesis catalyzed by two sphingosine kinases, denoted SphK1 SphK2. Many stimuli activate translocate the plasma membrane mechanisms are dependent on phosphorylation. Much less known about...
Abstract Sphingosine-1-phosphate is a potent lipid mediator formed by phosphorylation of sphingosine, metabolite sphingolipids, catalyzed two sphingosine kinase (SphK) isoenzymes, SphK1 and SphK2. Expression SphK2, which enriched in the nucleus MCF7 human breast cancer cells, increased expression cyclin-dependent inhibitor p21 but had no effect on p53 or its phosphorylation. The anticancer drug doxorubicin known to increase via p53-dependent p53-independent mechanisms. Down-regulation...
Sphingosine-1-phosphate (S1P), a ligand for 5 specific receptors, is potent lipid mediator that plays important roles in lymphocyte trafficking and immune responses. S1P produced inside cells therefore must be secreted to exert its effects through these receptors. Spinster 2 (Spns2) one of the cell surface transporters thought secrete S1P. We have shown Spns2 can export endogenous from also dihydro-S1P, which active at all Moreover, Spns2–/– mice decreased levels both phosphorylated...
Abstract Estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and does not respond to conventional hormonal therapies. Strategies that lead re-expression of ERα could sensitize ERα-negative cancers selective ER modulators. FTY720 (fingolimod, Gilenya), a sphingosine analog, the Food Drug Administration (FDA)-approved prodrug for treatment multiple sclerosis also has anticancer actions are yet well understood. We found phosphorylated in cells by nuclear kinase 2...
Sphingosine 1-phosphate (S1P), produced by two sphingosine kinase isoenzymes, denoted SphK1 and SphK2, is the ligand for a family of five specific G protein-coupled receptors that regulate cytoskeletal rearrangements cell motility. Whereas many growth factors stimulate SphK1, much less known regulation SphK2. Here we report epidermal factor (EGF) stimulated SphK2 in HEK 293 cells. This first example an agonist-dependent Chemotaxis cells toward EGF was inhibited N,N-dimethylsphingosine,...