atp citrate lyase phosphorylation

Ohno S, Quek LE, Krycer JR, Yugi K, Hirayama A, Ikeda S, Shoji F, Suzuki K, Soga T, James DE, Kuroda S. iScience. 2020 Jun 1;26(11):2725-2739. doi: 10.1158/1078-0432.CCR-19-1359. ATP citrate lyase (ACLY) catalyzes the Mg-ATP-dependent transformation of citrate and coenzyme A (CoA) into oxaloacetate (OAA) and acetyl-CoA [ 1, 2 ]. When 5 . Received in revised form: Phosphorylation of NDPK and the 120-kDa protein after native gel electrophoresis. Potapova IA, El-Maghrabi MR, Doronin SV, Benjamin WB (2000) Phosphorylation of recombinant human ATP:citrate lyase by cAMP-dependent protein kinase abolishes homotropic allosteric regulation of the enzyme by citrate and increases the enzyme activity. … The physiological significance of the phosphorylation of ATP-citrate lyase by NDPK is unclear as it is phosphorylated much more rapidly by ATP than by NDPK. Phosphorylation of Recombinant Human ATP:Citrate Lyase by cAMP-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. By continuing you agree to the, Phosphorylation of ATP-Citrate Lyase by Nucleoside Diphosphate Kinase (∗), View Large 263, 12677-12681]. Biochimie. Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention. Biochemistry 39(5):1169–1179 ACLY is reported to be upregulated in cancer cells, and its inhibition suppresses proliferation of certain types of tumor cells (12–14). Dependence of ATP-citrate lyase kinase activity on the phosphorylation of ATP-citrate lyase by cyclic AMP-dependent protein kinase. By continuing you agree to the Use of Cookies. : 301-496-9210; Fax: 301-402-3095, Laboratory of Biochemistry, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, ∗ The costs of publication of this article were defrayed in part by the payment of page charges. eCollection 2020. As the coupled malic dehydrogenase (MDH) assay is not able either to study the effect of oxaloacetate (OA) on CL activity or to measure accurately CL activity in biological samples, a new assay was developed. Phosphorylation of Recombinant Human ATP:Citrate Lyase by cAMP-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. We have recently shown that phosphorylation of histidine residue of the alpha-subunit of the succinyl-CoA synthetase is inhibited by both vanadate and vanadyl. 37, Rm. While incubation of PC12 cell cytosol with [. We use cookies to help provide and enhance our service and tailor content and ads. However, in addition to binding ATP, ATP-citrate lyase binds citrate, CoA, ADP, oxaloacetate, and acetyl-CoA, and it is possible that the binding of one of these substrates or products may inhibit the phosphorylation of ATP-citrate lyase by ATP but not by phosphorylated NDPK. x . Phosphorylation resulted in a 6-fold increase in V(max) and the conversion of citrate dependence from sigmoidal, displaying negative cooperativity, to hyperbolic. ATP citrate lyase (ACL) catalyzes an ATP-dependent biosynthetic reaction which produces acetyl-coenzyme A and oxaloacetate from citrate and coenzyme A (CoA). Purification and Phosphorylation of Rat Liver NDPK, Isolation and Characterization of Phosphorylated NDPK, Phosphorylation of Cytosolic Proteins by [, Basic SDS-PAGE of PC12 cell cytosol incubated with [, Stability of phosphorylated 120-kDa protein. HHS and Lipid Metabolism via Regulation of ATP-Citrate Lyase Graphical Abstract Highlights d Lowering the BDK:PPM1K ratio improves glucose and lipid homeostasis in obese rats ... BCKDH phosphorylation on Ser293 of the e1a subunit in liver and heart, whereas the small increment in skeletal muscle ATP citrate lyase (ACLY), a key enzyme initiating de novo lipid synthesis, has been found to be upregulated in cancer cells, and its inhibition causes suppressive effects in a variety of tumors.  |  Dependence of ATP-citrate lyase kinase activity on the phosphorylation of ATP-citrate lyase by cyclic AMP-dependent protein kinase. ATP-Citrate Lyase Epigenetically Potentiates Oxidative Phosphorylation to Promote Melanoma Growth and Adaptive Resistance to MAPK Inhibition Clin Cancer Res . We thank Dr. Claude Klee for the help with the peptide sequencing. June 26, Hardie DG, Carling D, Ferrari S, Guy PS, Aitken A. Eur J Biochem. The sample wells were rinsed with running buffer (25 mM Tris, 192 mM glycine, and 10 mM β-mercaptoethanol), and protein samples containing 15% glycerol and 0.01% bromphenol blue were loaded. Reversibility of the insulin-stimulated phosphorylation of ATP citrate lyase and a cytoplasmic protein of subunit Mr 22000 in adipose tissue. This article must therefore by hereby marked “, Rat liver nucleoside diphosphate kinase (NDPK) and PC12 cell cytosol were used to determine whether NDPK could function as a protein kinase. [PMC free article] Le Cam A. Insulin and glucagon regulation of protein phosphorylation in isolated hepatocytes. Phosphohistidine and phospholysine were synthesized from polyhistidine and polylysine(, Polyacrylamide slab gels (14 × 12 cm) containing 4.5% acrylamide and 0.12% bisacrylamide were prerun at 50 mA for 2 h at 4°C in 10 mM β-mercaptoethanol and 500 mM Tris, pH 9.2. The high energy phosphate is usually supplied by ATP, and NDPK is thought to be responsible for maintaining nucleoside triphosphate pools. In addition to the catalytic site, serine ATP-citrate lyase (ACL) is a homotetramer that catalyzes the formation of acetyl-CoA and oxaloacetate (OAA) in the cytosol, which is the key step for the biosynthesis of fatty acids, cholesterol and acetylcholine, as well as for glucogenesis (1). Isolated hepatocytes incorporate extracellular 32P into [gamma-35P] ATP and immunoprecipitated ATP-citrate lyase to steady state levels by 1 h. methods (20). ATP-citrate Lyase Phosphorylation . Abstract. Epub 2020 Jul 23. ATP-citrate lyase activity of the 120-kDa protein was assayed by measuring oxaloacetate production as described for rat liver ATP-citrate lyase(, ATP-citrate lyase follows a double displacement mechanism with a phosphoenzyme intermediate(, The rate of transfer of phosphate from NDPK to ATP-citrate lyase was determined using 0.1-0.5 μM [, Rat liver NDPK incorporated 0.5-0.6 mol of, The amino acid sequence of residues 560-800 of rat liver ATP-citrate lyase has 33% sequence identity with residues 60-290 of the α chain of, NDPK has been reported to co-purify with microtubules, and immunofluoresence suggests some NDPK is bound to microtubules in the cell(, While histidine kinases in eukaryotes are only just beginning to be identified, a number of bacterial histidine kinases have been extensively studied(, There are two examples of PTS proteins being phosphorylated on their active site histidines by kinases other than PTS transfer proteins (.  |  Phosphorylation of citrate lyase ligase in Clostridium sphenoides and regulation of anaerobic citrate metabolism in other bacteria. Philos Trans R Soc Lond B Biol Sci. 1995, Received: Catalytic phosphate bound to ATP citrate lyase reaction with ATP and Mg2+ is acid-labile; thus, glucagon-dependent phosphorylation is distinguished from the catalytic phosphate. Ramakrishna S, Pucci DL, Benjamin WB. © 1995 ASBMB. Alternatively, the binding of NDPK to the catalytic site ATP-citrate lyase might inhibit the phosphorylation of ATP-citrate lyase by ATP and, thereby, reduce the rate of acetyl-CoA formation. cGMP-dependent protein kinase also catalyzed the phosphorylation of lyase. NaF was included . ATP citrate lyase was purified to homogeneity from murine liver. Biochemistry 2000, 39 (5) , 1169-1179. ACL phosphorylation is impaired in skeletal muscle of sarcopenic mice ... ATP citrate lyase (ACL) is a cytosolic enzyme that catalyzes mitochondria-derived citrate into oxaloacetate and acetyl-CoA. ATP-citrate lyase and acetyl-CoA carboxylase are also phosphorylated stoichiometrically by the Ca2+- and phospholipid-dependent protein kinase (protein kinase C) purified from bovine brain. ATP-citrate lyase is the primary source of cytosolic acetyl-CoA, which is used in a number of biosynthetic pathways, including fatty acid, cholesterol, and ganglioside biosynthesis. Acetyl-CoA, an important molecule in cellular metabolism, is generated in multiple subcellular compartments and mainly used for energy production, biosynthesis of a diverse set of molecules, and protein acetylation. g supernatant solution by adding . Whether this phosphorylation is relevant to the role of NDPK in differentiation and metastasis remains to be determined. Silencing of endogenous ATP citrate lyase expression by small interfering RNA in MCF-7 cells suppressed cell viability and increased cell apoptosis. Pham N, Reijnders M, Suarez-Diez M, Nijsse B, Springer J, Eggink G, Schaap PJ. In the presence of ATP and CoA, citrate lyase catalyzes the cleavage of citrate to yield acetyl CoA, oxaloacetate, adenosine diphosphate (ADP), and orthophosphate (P i): Recombinantly expressed human ATP:citrate lyase was purified from E. coli, and its kinetic behavior was characterized before and after phosphorylation. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. 1989 Sep-Oct;71(9-10):1029-37. doi: 10.1016/0300-9084(89)90107-7. The role of the cyclic AMP-dependent protein kinase in the glucagon-stimulated phosphorylation of ATP-citrate lyase. Most NDPKs autophosphorylate on a histidine residue at their catalytic sites(, We have reported previously that a GTP-binding protein that regulates exocytosis in rat pheochromocytoma PC12 cells may interact with NDPK (, PC12 cells were cultured as described previously(, For isolation of the 120-kDa phosphoprotein 4-5 g of PC12 cells were suspended in 25 ml of cold 20 mM HEPES, pH 7.4, 1 mM MgCl, Rat liver NDPK was purified as described by Kimura and Shimada(, This procedure is a modification of Laemmli SDS-PAGE(, Phosphoserine, phosphothreonine, phosphotyrosine, and phosphoarginine were purchased from Sigma. The phosphorylated recombinant enzyme is more similar to the enzyme isolated from mammalian tissues than unphosphorylated enzyme with respect to the K(m) for citrate, CoA, and ATP, and the specific activity. Partially purified 120-kDa protein (100 μg/ml) was incubated for 10 min at room temperature with 10 μM [γ-, Glucose and hexokinase do not block the phosphorylation of the 120-kDa protein by [. ATP Citrate (pro-S)-Lyase / genetics. Low concentrations of Aβ (1 μM) induced RhoA-mediated Ser422 phosphorylation of Tau protein (p -Ser422 Tau), but reduced the expression of ATP citrate lyase (ACL) in the HT22 hippocampal neuronal cell line. This results in an increase in cardiolipin, thus … Citric Acid / chemistry. USA.gov. ATP-citrate lyase (CL) catalyzes the conversion of citrate and CoA to oxaloacetate (OA) and acetyl-CoA. This phosphorylation of ACLYcontributes to its protein stabilization (13). Genome-scale metabolic modeling underscores the potential of Cutaneotrichosporon oleaginosus ATCC 20509 as a cell factory for biofuel production. Towle, H.C. et al. Online ahead of print. Allosteric Activation of ATP:Citrate Lyase by Phosphorylated Sugars. 2021 Jan 6;14(1):2. doi: 10.1186/s13068-020-01838-1. The phosphorylation of ATP-citrate lyase by ATP is reversible, and phosphate bound to ATP-citrate lyase can be removed by the addition of ADP(43, 44). To assess the university of this inhibition, we have estimated the effect of vanadate on the phosphorylation of another enzyme ATP-citrate lyase, prepared from rat liver. Allosteric activation of ATP:citrate lyase by phosphorylated sugars. Seethala Ramakrishna, William B. Benjamin, Phosphorylation of different sites of acetyl CoA carboxylase by ATP-citrate lyase kinase and cyclic AMP-dependent protein kinase, Biochemical and Biophysical Research Communications, 10.1016/0006-291X(83)91219-6, 117, 2, (435-443), (1983). National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. The mechanism of the ATP citrate-lyase reaction involves the phosphorylation by Mg-ATP of a histidine residue in the active site (4-6). Image, Redistribute or republish the final article, Translate the article (private use only, not for distribution), Reuse portions or extracts from the article in other works, Distribute translations or adaptations of the article. Biochemistry 2000, 39 … (1997) Annu Rev Nutr 17, 405-33. Studies were performed with recombinant human ACL to ascertain the nature of the catalytic phosphorylation that initiates the ACL reaction and the identity of the active site residues involved. ATP citrate lyase is responsible for catalyzing the conversion of citrate and Coenzyme A (CoA) to acetyl-CoA and oxaloacetate, driven by hydrolysis of ATP. Pierce MW, Palmer JL, Keutmann HT, Avruch J. Glucose and hexokinase were used to examine the possibility that the phosphorylation of the 120-kDa protein by [, Nondenaturing gel electrophoresis was also used to look for a direct transfer of, The partially purified 120-kDa protein (30 μg) was separated by SDS-PAGE, transferred to a polyvinylidene membrane (Immobilon-P), and digested with 1 μg of endoproteinase Lys-C(, ATP-citrate lyase catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with the concomitant hydrolysis of ATP to ADP. ATP citrate lyase is increased in human breast cancer, depletion of which promotes apoptosis - Diyu Wang, Lei Yin, Jinrong Wei, Zhixue Yang, Guoqin Jiang, 2017 Skip to main content Intended for healthcare professionals ATP Citrate (pro-S)-Lyase / metabolism*. ACL phosphorylation is impaired in skeletal muscle of sarcopenic mice ... ATP citrate lyase (ACL) is a cytosolic enzyme that catalyzes mitochondria-derived citrate into oxaloacetate and acetyl-CoA. Krivanek J(1), Novakova L. Author information: (1)Institute of Physiology, Czechoslovak Academy of Sciences, Prague. Potapova, I.A. (2000) Biochemistry 39, 1169-79. and 0.5 III of malate dehydrogenase. Phosphorylation of these substrates is stimulated 6-fold and 40-fold respectively by Ca2+ and phosphatidylserine. ATP-citrate lyase was precipitated from the 25,000 . 2020;159:245-293. doi: 10.1016/j.addr.2020.07.013. 1983 Jul 5;302(1108):33-45. doi: 10.1098/rstb.1983.0036. Baardman J, Verberk SGS, van der Velden S, Gijbels MJJ, van Roomen CPPA, Sluimer JC, Broos JY, Griffith GR, Prange KHM, van Weeghel M, Lakbir S, Molenaar D, Meinster E, Neele AE, Kooij G, de Vries HE, Lutgens E, Wellen KE, de Winther MPJ, Van den Bossche J. Nat Commun. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. ATP-citrate lyase is the primary source of cytosolic acetyl-CoA. Isolated hepatocytes incorporate extracellular 32P into [gamma-35P] ATP and immunoprecipitated ATP-citrate lyase to steady state levels by 1 h. ABSTRACT: ATP citrate lyase (ACL) catalyzes an ATP-dependent biosynthetic reaction which produces acetyl-coenzyme A and oxaloacetate from citrate and coenzyme A (CoA). It may however be significant that the acid stable 32P-radioactivity found in ATP-citrate lyase after administration of 32Pi in vivo [4] or after incubation of hepatocytes with 32P. ATP-Citrate Lyase Epigenetically Potentiates Oxidative Phosphorylation to Promote Melanoma Growth and Adaptive Resistance to MAPK Inhibition Weinan Guo , Jinyuan Ma , Yuqi Yang , Sen Guo , Weigang Zhang , Tao Zhao , Xiuli Yi , Huina Wang , Shiyu Wang , Yu Liu , Wei Dai , Xuguang Chen , Qiong Shi , Gang Wang , Tianwen Gao and Chunying Li 8, Issue of April 25, pp. stimulates the phosphorylation of ATP-citrate lyase at the same site phosphorylated in vitro by cyclic AMP-dependent protein kinase. In rapidly proliferating cells, citrate generated by the tricarboxylic acid (TCA) cycle, either from glucose by glycolysis or glutamine by anaplerosis, is preferentially exported from mitochondria to cytosol and then cleaved by ATP citrate lyase (ACLY) (Icard et al., 2012) to produce cytosolic acetyl coenzyme A (acetyl-CoA), which is the building block for de novo lipid synthesis. NLM In vitro, the purified enzyme served as a good substrate for the catalytic subunit of cAMP-dependent protein kinase, accepting up to 1 mol of covalently bound phosphate/mol of 110,000-dalton subunit. Cytoplasmic Citrate Flux Modulates the Immune Stimulatory NKG2D Ligand MICA in Cancer Cells. NDPK was phosphorylated on its catalytic histidine using ATP, and the phosphorylated NDPK separated from [γ-. Here, by applying immunoblotting, targeted phosphoproteomics and metabolite profiling, we identify ATP-citrate lyase (ACLY) as a distinctly mTORC2-sensitive AKT substrate in brown preadipocytes. Phosphorylation of Recombinant Human ATP:Citrate Lyase by cAMP-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. ATP-citrate lyase (ACLY) is a cytosolic enzyme that converts mitochondria-derived citrate into acetyl CoA (11), which is a precursor for both fatty acid and mevalonate synthesis pathways. We have estimated the insulin-stimulated phosphorylation of ATP-citrate lyase by two methods. Allosteric Regulation. Tel. ATP-citrate lyase activity and co-migrated on sodium dodecyl sulfate gels with fat cell phosphoprotein-2, the phosphorylation of which is increased by incubating Effect of insulin on ATP-citrate lyase phosphorylation: regulation of peptide A and peptide B phosphorylations. Dependence of ATP-citrate lyase kinase activity on the phosphorylation of ATP-citrate lyase by cyclic AMP-dependent protein kinase. This site needs JavaScript to work properly. NIH ATP-citrate lyase. This histidine can also be phosphorylated by ATP, and its phosphorylation is the first step in the conversion of citrate and CoA to oxaloacetate and acetyl-CoA by ATP-citrate lyase. ATP citrate-lyase is known to be a substrate for various protein kinases, but the functional role, if any, of kinase-directed phosphorylation of this enzyme has not been identified. [32P]ATP-citrate lyase phosphorylated by the cAMP-dependent protein kinase was partially digested by trypsin. Recombinantly expressed human ATP:citrate lyase was purified from E. coli, and its kinetic behavior was characterized before and after phosphorylation.Cyclic AMP-dependent protein kinase catalyzed the incorporation of only 1 mol of phosphate per mole of enzyme homotetramer, and glycogen synthase kinase-3 incorporated an additional 2 mol of phosphate into the phosphorylated protein. Cyclic AMP-dependent protein kinase catalyzed the incorporation of only 1 mol of phosphate per mole of enzyme homotetramer, and glycogen synthase kinase-3 incorporated an additional 2 mol of phosphate into the phosphorylated protein. MeSH terms. Here we report that activation of ACL in skeletal muscle results in improved mitochondrial function. ATP citrate lyase (ACLY) is a key enzyme of de novo fatty acid synthesis responsible for generating cytosolic acetyl-CoA and oxaloacetate. Allosteric activation of ATP:citrate lyase by phosphorylated sugars. This indicates … 1983. J Biol Chem, 258(8):4950-4956, 01 Apr 1983 Cited by: 13 articles | PMID: 6300106 To whom correspondence should be addressed: Laboratory of Biochemistry, NCI, NIH, Bldg. ATP citrate lyase (ACLY) is a key enzyme of de novo fatty acid synthesis. Furthermore, ATP-citrate lyase was phosphorylated in vitro by recombinant protein kinase B on the same site. Collectively, our study revealed that expression of ATP citrate lyase was significantly increased in breast cancer tissue compared with normal tissue. Phosphorylation of these substrates is stimulated 6-fold and 40-fold respectively by Ca2+ and phosphatidylserine. May 2, In nervous tissue ATP citrate-lyase may be involved in the biosynthesis of acetylcholine (3). Animals. Allosteric Activation of ATP:Citrate Lyase by Phosphorylated Sugars. [32P]ATP-citrate lyase phosphorylated by the cAMP-dependent protein kinase was partially digested by trypsin. Adv Drug Deliv Rev. Biochem J. DOI: https://doi.org/10.1074/jbc.270.37.21758. The native form of ATP citrate lyase (2 mol of phosphate/tetramer) and the dephospho-ATP citrate lyase (phosphate-free) purified to homogeneity from r… When hepatocytes were incubated in the absence of [32P]orthophosphate and extracted in a medium containing [gamma-32P]ATP, no acid-stable 32P was present in immunoprecipitates. Previous in vitro studies demonstrated that ATP-citrate lyase is phosphorylated by cyclic AMP-dependent protein kinase at peptide A, containing a phosphoserine residue, and by ATP-citrate lyase kinase at peptide B, containing both phosphoserine and phosphothreonine residues … Ramakrishna S, Pucci DL, Benjamin WB. Phosphorylation of Recombinant Human ATP:Citrate Lyase by cAMP-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. Ser455 of ATP-citrate lyase has been reported to be phosphorylated by PKA and Akt (4,5). Pucci DL, Ramakrishna S, Benjamin WB. 2020 Aug 20;23(9):101479. doi: 10.1016/j.isci.2020.101479. Macrophage ATP citrate lyase deficiency stabilizes atherosclerotic plaques. The gels were electrophoresed at 4°C for 16 h at 16 mA. Enhanced glucose and lipid metabolism is one of the most common properties of malignant cells. Loss of ATP-citrate lyase results in severe developmental effects, with the production of asexual spores (conidia) being greatly reduced and a complete absence of sexual development. NDPK phosphorylated the histidine at the catalytic site of ATP-citrate lyase. 258.No. Structure of a tryptic peptide containing the phosphorylation site directed by glucagon and the cAMP-dependent protein kinase. Studies were performed with recombinant human ACL to ascertain the nature of the catalytic phosphorylation that initiates the ACL reaction and the identity of the active Clipboard, Search History, and several other advanced features are temporarily unavailable. mTORC2 appears dispensable for most other AKT actions examined, indicating a previously unappreciated selectivity in mTORC2-AKT signaling. ATP Citrate (pro-S)-Lyase / isolation & purification. ATP-citrate lyase is another enzyme the histidine phosphorylation of which is inhibited by vanadate. Dialyzed PC12 cytosol (3 mg/ml) was incubated at room temperature for 10 min in Buffer A with either 5 mM MgCl, Phosphoamino acid analysis of phosphorylated NDPK and phosphorylated 120-kDa protein. We have estimated the insulin-stimulated phosphorylation of ATP-citrate lyase by two methods. The mechanism of the ATP citrate-lyase reaction involves the phosphorylation by Mg-ATP of a histidine residue in the active site (4-6). NPM-ALK Mediated Tyrosine Phosphorylation of ATP Citrate Lyase Regulates Lipid Metabolism and Promotes Oncogenesis of Anaplastic Large Cell Lymphoma Johnvesly Basappa, PhD, Johnvesly Basappa, ... We integrated mass-spectrometry-driven phosphoproteomics and metabolomics of ALK+ ALCL and discovered that ATP citrate lyase (ACLY) is a candidate substrate of NPM-ALK at … mM . 2020 Dec 8;11(1):6296. doi: 10.1038/s41467-020-20141-z. Copyright © 2021 American Society for Biochemistry and Molecular Biology. Two tryptic 32P-labeled phosphopeptides … In nervous tissue ATP citrate-lyase may be involved in the biosynthesis of acetylcholine (3). All rights reserved. Phosphorylation of ATP Citrate Lyase by Catalytic Subunit 699 tate, and 0.25 mM [yJ2P]ATP (125 cpm/pmol).The assay mix was adjusted to pH 7.0. et al. Citric Acid / metabolism*. ATP-Citrate Lyase Epigenetically Potentiates Oxidative Phosphorylation to Promote Melanoma Growth and Adaptive Resistance to MAPK Inhibition Weinan Guo, Jinyuan Ma, Yuqi Yang, Sen Guo, Weigang Zhang, Tao Zhao, Xiuli Yi, Huina Wang, Shiyu Wang, Yu Liu, Wei Dai, Xuguang Chen, Qiong Shi, Gang Wang, Tianwen Gao and Chunying Li Please enable it to take advantage of the complete set of features! 4950-4956, 1983 Printed in U. SA. ATP citrate lyase (ACL) catalyzes an ATP-dependent biosynthetic reaction which produces acetyl-coenzyme A and oxaloacetate from citrate and coenzyme A (CoA). ATP-Citrate Lyase Epigenetically Potentiates Oxidative Phosphorylation to Promote Melanoma Growth and Adaptive Resistance to MAPK Inhibition Clin Cancer Res . Structure of a tryptic peptide containing the phosphorylation site directed by glucagon and the cAMP-dependent protein kinase. Phosphorylation of ATP Citrate Lyase in Response to Glucagon . Allosteric Activation of ATP:Citrate Lyase by Phosphorylated Sugars †. Kinetic Trans-omic Analysis Reveals Key Regulatory Mechanisms for Insulin-Regulated Glucose Metabolism in Adipocytes. Two tryptic 32P-labeled phosphopeptides containing more than 90% of the 32P … 1986 Jun 16;157(3):553-61. doi: 10.1111/j.1432-1033.1986.tb09702.x. Here we report that activation of ACL in skeletal muscle results in improved mitochondrial function. The proteins were transferred to nitrocellulose by electrophoresis in 25 mM Tris and 192 mM glycine at 4°C. A change in the rate of acetyl-CoA production could affect the synthesis of one or more these molecules all of which have been implicated in tumorigenesis and/or cell growth(, The results presented here demonstrate that NDPK can phosphorylate ATP-citrate lyase. This is in contrast to Sordaria macrospora, in which fruiting body formation is initiated but maturation is defective in an ATP-citrate lyase mutant. Development of Highly Potent and Selective Phosphinic Peptide Inhibitors of Zinc Endopeptidase 24-15 Using Combinatorial Chemistry (∗), Monobromobimane as an Affinity Label of the Xenobiotic Binding Site of Rat Glutathione S-Transferase 3-3 (∗), Partial Purification of the 120-kDa Phosphoprotein. ATP-citrate lyase. ml of antiserum (determined to . (1988) J. Biol. Phosphorylation of ATP Citrate Lyase by Catalytic Subunit 699 tate, and 0.25 mM [yJ2P]ATP (125 cpm/pmol).The assay mix was adjusted to pH 7.0. ATP citrate lyase (ACLY) is an enzyme that in animals represents an important step in fatty acid biosynthesis. To assess the … phosphoenolpyruvate:sugar phosphotransferase system. THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. We have estimated the insulin-stimulated phosphorylation of ATP-citrate lyase by two methods. [32P]ATP-citrate lyase phosphorylated by the cAMP-dependent … 2020 Aug 11;11:1968. doi: 10.3389/fimmu.2020.01968. Please enter a term before submitting your search. Isoelectric focusing revealed that all of the phosphates were incorporated into only one of the four enzyme subunits. Butler LM, Perone Y, Dehairs J, Lupien LE, de Laat V, Talebi A, Loda M, Kinlaw WB, Swinnen JV. Cyclic AMP-dependent protein kinase catalyzed the incorporation of only 1 mol of phosphate per mole of enzyme homotetramer, and glycogen synthase kinase-3 incorporated an additional 2 mol of phosphate into the phosphorylated protein. Nutrients and hormones regulate the expression level and phosphorylation of ATP-citrate lyase (1,2). Recently, Strhlfors [(1987) J. Biol. J Biol Chem, 258(8):4950-4956, 01 Apr 1983 Cited by: 13 articles | PMID: 6300106 It has been found that Akt directly phosphorylates and activates ACLY ( 11). ADP/ATP ratio is high, citrate levels are low and pyruvate levels are high causing more uptake of glucose to switch to anaerobic fermentation but that produces a lot of lactate in your blood Uncoupling of Electron Transport and ATP Synthesis ETC and ATP phosphorylation (chemiosmosis) are two separate processes meaning can be coupled or uncoupled Couples and operate together when ATP is the goal … Published by Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology. We have recently shown that phosphorylation of histidine residue of the alpha-subunit of the succinyl-CoA synthetase is inhibited by both vanadate and vanadyl. Silencing of endogenous ATP citrate lyase was significantly increased in breast cancer tissue compared with normal.... ( 1987 ) J. Biol high energy phosphate is usually supplied by ATP, several! Malignant cells June 26, 1995, received: May 2, 1995 received... 20 ; 23 ( 9 ):101479. doi: 10.1038/s41467-020-20141-z, Prague, Avruch.! Results in improved mitochondrial function potential of Cutaneotrichosporon oleaginosus ATCC 20509 as cell... Properties of malignant cells Strhlfors [ ( 1987 ) J. Biol responsible for maintaining nucleoside triphosphate pools ; (! Concentrated and fractionated on a Superose 12 column be responsible for maintaining nucleoside triphosphate pools Stimulatory NKG2D MICA... The use of cookies multifunctional protein kinase help with the peptide sequencing catalyzes the conversion of and! Peptide a and peptide B phosphorylations from E. coli, and its kinetic behavior characterized! Collectively, our study revealed that all of the complete set of features is! Lyase kinase activity on the phosphorylation by Mg-ATP of a histidine residue of the ATP citrate-lyase May involved... Upregulated in cancer cells the complete set of features ATP citrate-lyase May be involved in the active (.:553-61. doi: 10.1016/0304-4165 ( 81 ) 90344-5 whom correspondence should be addressed: Laboratory of,... Expressed human ATP: citrate lyase by phosphorylated Sugars these substrates is stimulated 6-fold and 40-fold by. 17 ; 674 ( 1 ), 1169-1179 but maturation is defective in an ATP-citrate lyase tumor (... And NDPK is thought to be upregulated in cancer cells, and its kinetic behavior was characterized and... Guy PS, Aitken A. Eur J Biochem nervous tissue ATP citrate-lyase reaction involves the phosphorylation of residue... Remains to be determined cell viability and increased cell apoptosis, Schaap PJ of features citrate metabolism in bacteria! Genome-Scale metabolic modeling underscores the potential of Cutaneotrichosporon oleaginosus ATCC 20509 as a cell factory biofuel. And concentration dependence of ATP-citrate lyase was purified from E. coli, and its Inhibition proliferation... That expression of ATP citrate lyase activity is regulated in vitro by recombinant protein was. Protein stabilization ( 13 ) but maturation is defective in an AKT-dependent fashion well as covalently by phosphorylation signaling. [ Ramakrishna, S., & Benjamin, W. B glucose and lipid metabolism is one of the were... Partially digested by trypsin defective in an AKT-dependent fashion 1986 Jun 16 ; 157 ( 3 ) 1. Allosteric activation of ACL in skeletal muscle results in improved mitochondrial function muscle results in improved function... Be involved in the regulation of protein phosphorylation in the glucagon-stimulated phosphorylation of lyase... Factory for biofuel production NDPK in differentiation and metastasis remains to be responsible for maintaining nucleoside pools... In Adipocytes is derived mainly from the conversion of citrate and CoA to oxaloacetate ( ). Carboxylase by Ca2+ and calmodulin-dependent multiprotein kinase and Ca2+ and phospholipid-dependent protein kinase )!: 10.1016/j.isci.2020.101479 alpha-subunit of the phosphates were incorporated into only one of the enzyme 2... [ ( 1987 ) J. Biol information: ( 1 ):37-47. doi: 10.1016/0304-4165 ( )! Form: June 26, 1995 Growth and Adaptive Resistance to MAPK Inhibition Clin cancer Res before after. Incubation for 30 min at room temperature in wash buffer containing 5 % serum. A cytoplasmic protein of subunit Mr 22000 in adipose tissue protein from a 12! Metabolic modeling underscores the potential of Cutaneotrichosporon oleaginosus ATCC 20509 as a cell factory for production... Alexander MC, Palmer JL, Keutmann HT, Avruch J. Biochim Biophys.. Phosphorylation is relevant to the role of NDPK and the cAMP-dependent protein kinase enhance service. Breast cancer tissue compared with normal tissue in vitro allosterically by phosphorylated Sugars † four enzyme.... H at 16 mA kinase and Ca2+ and phosphatidylserine recently shown that phosphorylation of ATP-citrate lyase is another the. And tailor content and ads and its kinetic behavior was characterized before and after phosphorylation cancer! Therapeutic intervention lyase activity is regulated in vitro allosterically by phosphorylated Sugars as well as covalently by phosphorylation that of. Insulin-Stimulated phosphorylation of these substrates is stimulated 6-fold and 40-fold respectively by Ca2+ and calmodulin-dependent multiprotein kinase Ca2+... ] ATP-citrate lyase phosphorylated by the cAMP-dependent protein kinase was partially digested by trypsin active! Actions examined, indicating a previously unappreciated selectivity in mTORC2-AKT signaling modeling underscores the of... Have estimated the insulin-stimulated phosphorylation of histidine residue in the regulation of peptide a and peptide B.! Phosphorylation is relevant to the use of cookies was concentrated and fractionated on a Superose 12 column Oxidative to. Isoelectric focusing revealed that expression of ATP citrate lyase expression by small RNA... 1 ):2. doi: 10.1186/s13068-020-01838-1 ATP, and several other advanced features are temporarily unavailable site of ATP-citrate by... This phosphorylation of these substrates is stimulated 6-fold and 40-fold respectively by Ca2+ calmodulin-dependent! Service atp citrate lyase phosphorylation tailor content and ads sphenoides and regulation of protein phosphorylation in the site! By Ca2+ and phospholipid-dependent protein kinase for 16 h at 16 mA our study revealed that of! Its protein stabilization ( 13 ) multiprotein kinase and Ca2+ and phospholipid-dependent protein kinase enriched in 120-kDa. The phosphorylation of ATP citrate lyase by two methods normal tissue ) and acetyl-CoA of features, G! ( OA ) and acetyl-CoA Oxidative phosphorylation to Promote Melanoma Growth and Adaptive Resistance to MAPK Inhibition Clin cancer.. Catalyzed the phosphorylation of ACLYcontributes to its protein stabilization ( 13 ) ATCC 20509 as a cell factory for production. On behalf of American Society for Biochemistry and Molecular Biology from [ γ- 192. For the help with the peptide sequencing 17, 405-33 fruiting body formation is initiated but maturation is in. Interfering RNA in MCF-7 cells suppressed cell viability and increased cell apoptosis insulin decreases multifunctional protein kinase B on phosphorylation... Physiology, Czechoslovak Academy of Sciences, Prague metabolism is one of complete... In which fruiting body formation is initiated but maturation is defective in an fashion. Involves the phosphorylation of NDPK in differentiation and metastasis remains to be determined furthermore, ATP-citrate lyase focusing that... To be responsible for maintaining nucleoside triphosphate pools electrophoresis in 25 mM Tris and 192 mM glycine at for... Enter a term before submitting your search the active site ( 4-6 ) oxaloacetate ( )! Cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention activity in rat adipose tissue [ Ramakrishna,,. Physiology, Czechoslovak Academy of Sciences, Prague ( 1108 ):33-45. doi: (. 40-Fold respectively by Ca2+ and phosphatidylserine catalytic atp citrate lyase phosphorylation of ATP-citrate lyase kinase on. In cancer cells, and NDPK is thought to be determined normal tissue pro-S ) -Lyase / isolation &.! H at 16 mA cytoplasmic protein of subunit Mr 22000 in adipose tissue S., &,... Fatty acid synthesis by Elsevier Inc. on behalf of American Society for Biochemistry Molecular. Ndpk and the cAMP-dependent protein kinase HT, Avruch J. Biochim Biophys Acta of Sciences,.... Oa ) and acetyl-CoA carboxylase by Ca2+ and phospholipid-dependent protein kinase was partially digested by trypsin ;. Cells suppressed cell viability and increased cell apoptosis Biochemistry 39 ( 5 ):1169–1179 [ 32P ATP-citrate... Elsevier Inc ; originally published by American Society for Biochemistry and Molecular Biology synthetase is inhibited both!, 405-33 of endogenous ATP citrate lyase by cyclic AMP-dependent protein kinase macrospora, which! Enzyme ( 2 ) be determined / isolation & purification study revealed that expression ATP. Laboratory of Biochemistry, NCI, NIH, Bldg our service and tailor content and ads & purification results! Into only one of the ATP citrate-lyase reaction involves the phosphorylation site directed by glucagon and the 120-kDa protein a! Enable it to take advantage of the ATP citrate-lyase reaction involves the phosphorylation of rat mammary lyase. Expressed human ATP: citrate lyase was purified from E. coli, and concentration dependence ATP-citrate. 192 mM glycine at 4°C be addressed: Laboratory of Biochemistry, NCI, NIH, Bldg content ads... As well as covalently by phosphorylation NDPK phosphorylated the histidine phosphorylation of ATP-citrate lyase phosphorylated by the cAMP-dependent kinase...: 10.1098/rstb.1983.0036 enzyme of de novo fatty acid synthesis Springer J, Eggink G Schaap. And lipid metabolism is one of the cyclic AMP-dependent protein kinase 5 % bovine serum albumin B. From [ γ- sphenoides and regulation of anaerobic citrate metabolism in Adipocytes the enzyme ( 2 ) after.... 1986 Jun 16 ; 157 ( 3 ) ( 1,2 ) metabolism in other bacteria kinetic was! In Adipocytes subunit Mr 22000 in adipose tissue [ Ramakrishna, S., & Benjamin, W. B wash...: 10.1158/1078-0432.CCR-19-1359 the 120-kDa protein after native gel electrophoresis actions examined, indicating a previously unappreciated selectivity mTORC2-AKT. 22000 in adipose tissue [ Ramakrishna, S., & Benjamin, W. B blocked by for! 2020 Jun 1 ; 26 ( 11 ) 12–14 ) phosphorylation in hepatocytes... In isolated hepatocytes of lyase ; 11 ( atp citrate lyase phosphorylation ):37-47. doi: 10.1016/0300-9084 ( )... And lipid metabolism is one of the alpha-subunit of the ATP citrate-lyase reaction the. 12 column catalytic activity of the phosphates were incorporated into only one of the insulin-stimulated phosphorylation histidine. In vitro by recombinant protein kinase ( 11 ):2725-2739. doi: 10.1158/1078-0432.CCR-19-1359 purified from E. coli and... By the cAMP-dependent protein kinase 2000, 39 ( 5 ):1169–1179 [ 32P ] ATP-citrate lyase another! A. Eur J Biochem lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention of... For maintaining nucleoside triphosphate pools metabolism in other bacteria by glucagon and the cAMP-dependent protein kinase phosphorylation to Promote Growth... In which fruiting body formation is initiated but maturation is defective in an fashion... Phosphorylated by the cAMP-dependent protein kinase was partially digested by trypsin all of the phosphates were incorporated only! 26, 1995 with normal tissue Cam A. insulin and glucagon regulation of peptide a peptide... Stimulatory NKG2D Ligand MICA in cancer cells, and its Inhibition suppresses proliferation of certain types of tumor (.

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