Phosphorylation of ATP-Citrate Lyase by Nucleoside Diphosphate Kinase (*)

Rat liver nucleoside diphosphate kinase (NDPK) and PC12 cell cytosol were used to determine whether NDPK could function as a protein kinase. NDPK was phosphorylated on its catalytic histidine using ATP, and the phosphorylated NDPK separated from [γ-32P]ATP. The addition of phosphorylated NDPK to dialyzed PC12 cell cytosol resulted in the phosphorylation of a protein with a subunit molecular mass of about 120 kDa. This phosphorylation appeared to occur by a direct transfer of a phosphoryl group from the catalytic histidine of NDPK to a histidine on the 120-kDa protein. The 120-kDa protein was partially purified and shown by peptide sequencing to be ATP-citrate lyase. ATP-citrate lyase is the primary source of cytosolic acetyl-CoA. NDPK phosphorylated the histidine at the catalytic site of 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. The level of phosphorylation of PC12 cell ATP-citrate lyase by phosphorylated NDPK was comparable with that by ATP. Thus, in addition to its nucleoside diphosphate kinase activity, NDPK can function as a protein kinase.

[1]  J. Janin,et al.  Nucleoside Diphosphate Kinase , 1996, The Journal of Biological Chemistry.

[2]  M. Véron,et al.  Autophosphorylation of nucleoside diphosphate kinase on non‐histidine residues , 1994, FEBS letters.

[3]  L. Jacobs,et al.  Fatty acid synthesis: a potential selective target for antineoplastic therapy. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Stuart L. Schreiber,et al.  A mammalian protein targeted by G1-arresting rapamycin–receptor complex , 1994, Nature.

[5]  A. Chakrabarty,et al.  Characterization of nucleoside-diphosphate kinase from Pseudomonas aeruginosa: complex formation with succinyl-CoA synthetase. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[6]  M. Simon,et al.  Protein histidine kinases and signal transduction in prokaryotes and eukaryotes. , 1994, Trends in genetics : TIG.

[7]  E. Postel,et al.  Nucleoside diphosphate kinase enzyme activity of NM23-H2/PuF is not required for its DNA binding and in vitro transcriptional functions. , 1994, The Journal of biological chemistry.

[8]  P. Steeg,et al.  A serine phosphorylation of Nm23, and not its nucleoside diphosphate kinase activity, correlates with suppression of tumor metastatic potential. , 1993, The Journal of biological chemistry.

[9]  P. Wagner,et al.  Stimulation of secretion in permeabilized PC12 cells by adenosine 5'-[gamma-thio]triphosphate: possible involvement of nucleoside diphosphate kinase. , 1993, The Biochemical journal.

[10]  S. J. Flint,et al.  Human c-myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis. , 1993, Science.

[11]  A. Varki,et al.  Kinetic and spatial interrelationships between ganglioside glycosyltransferases and O-acetyltransferase(s) in human melanoma cells. , 1993, The Journal of biological chemistry.

[12]  T. Stephenson,et al.  Nm23 protein expression in ductal in situ and invasive human breast carcinoma. , 1993, Journal of the National Cancer Institute.

[13]  S. Inouye,et al.  Autophosphorylation of nucleoside diphosphate kinase from Myxococcus xanthus , 1993, Journal of bacteriology.

[14]  P. Steeg,et al.  Embryonic expression of nm23 during mouse organogenesis. , 1992, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[15]  L. Baggetto,et al.  Deviant energetic metabolism of glycolytic cancer cells. , 1992, Biochimie.

[16]  S. Nagataki,et al.  Expression in human hepatocellular carcinoma of nucleoside diphosphate kinase, a homologue of the nm23 gene product. , 1992, Journal of the National Cancer Institute.

[17]  J. Janin,et al.  X‐ray structure of nucleoside diphosphate kinase. , 1992, The EMBO journal.

[18]  I. Lascu,et al.  Nucleoside diphosphate kinase does not directly interact with tubulin nor microtubules. , 1992, Biochemical and biophysical research communications.

[19]  S. Hemmerich,et al.  Oligomeric structure and autophosphorylation of nucleoside diphosphate kinase from rat mucosal mast cells. , 1992, Biochemistry.

[20]  J. Strahler,et al.  Proliferation-related expression of p19/nm23 nucleoside diphosphate kinase. , 1992, The Journal of clinical investigation.

[21]  H. Magdelenat,et al.  Nucleoside diphosphate kinase/NM23 expression in breast cancer: Lack of correlation with lymph‐node metastasis , 1992, International journal of cancer.

[22]  J. Thiery,et al.  Overexpression of nucleoside diphosphate kinase (Nm23) in solid tumours. , 1991, European journal of cancer.

[23]  D. Lambeth,et al.  Apparent ATP-linked succinate thiokinase activity and its relation to nucleoside diphosphate kinase in mitochondrial matrix preparations from rabbit. , 1991, Biochimica et biophysica acta.

[24]  T. Wells.  ATP‐citrate lyase from rat liver , 1991 .

[25]  J. Strahler,et al.  High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N-myc gene amplification. , 1991, The Journal of clinical investigation.

[26]  J. Willson,et al.  Induction of nm23 gene expression in human colonic neoplasms and equal expression in colon tumors of high and low metastatic potential. , 1991, Journal of the National Cancer Institute.

[27]  A. Gilles,et al.  Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. , 1991, The Journal of biological chemistry.

[28]  L. Liotta,et al.  Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm3-transfected melanoma cells , 1991, Cell.

[29]  B Angus,et al.  Expression of the antimetastatic gene nm23 in human breast cancer: an association with good prognosis. , 1991, Journal of the National Cancer Institute.

[30]  T. Katada,et al.  Conversion of GDP into GTP by nucleoside diphosphate kinase on the GTP-binding proteins. , 1990, The Journal of biological chemistry.

[31]  R. Potter,et al.  Nucleoside diphosphate kinase from Xenopus oocytes; partial purification and characterization. , 1990, Biochimica et biophysica acta.

[32]  L. Liotta,et al.  A Drosophila gene that is homologous to a mammalian gene associated with tumor metastasis codes for a nucleoside diphosphate kinase , 1990, Cell.

[33]  N. Shimada,et al.  Evidence for complex formation between GTP binding protein(Gs) and membrane-associated nucleoside diphosphate kinase. , 1990, Biochemical and biophysical research communications.

[34]  C. Southan,et al.  Rat ATP citrate-lyase. Molecular cloning and sequence analysis of a full-length cDNA and mRNA abundance as a function of diet, organ, and age. , 1990, The Journal of biological chemistry.

[35]  P. Wagner,et al.  Thiophosphorylation causes Ca2+-independent norepinephrine secretion from permeabilized PC12 cells. , 1989, The Journal of biological chemistry.

[36]  L. Liotta,et al.  Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development , 1989, Nature.

[37]  A. Ninfa,et al.  Phosphorylation and dephosphorylation of a bacterial transcriptional activator by a transmembrane receptor. , 1989, Genes & development.

[38]  V. Weiss,et al.  Phosphorylation of nitrogen regulator I (NRI) of Escherichia coli. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[39]  J. Biggs,et al.  Molecular consequences of awdb3, a cell-autonomous lethal mutation of Drosophila induced by hybrid dysgenesis. , 1988, Developmental biology.

[40]  J E Talmadge,et al.  Evidence for a novel gene associated with low tumor metastatic potential. , 1988, Journal of the National Cancer Institute.

[41]  N. Shimada,et al.  Membrane-associated nucleoside diphosphate kinase from rat liver. Purification, characterization, and comparison with cytosolic enzyme. , 1988, The Journal of biological chemistry.

[42]  L. Hood,et al.  Internal amino acid sequence analysis of proteins separated by one- or two-dimensional gel electrophoresis after in situ protease digestion on nitrocellulose. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[43]  T. Ikeuchi,et al.  Characterization of nucleoside-diphosphate kinase-associated guanine nucleotide-binding proteins from HeLa S3 cells. , 1986, Biochimica et biophysica acta.

[44]  B. Sykes,et al.  Phosphorus-31 nuclear magnetic resonance study of the active site phosphohistidine and regulatory phosphoserine residues of rat liver ATP-citrate lyase. , 1985, Biochemistry.

[45]  P. Srere,et al.  Identification of ATP citrate lyase as a phosphoprotein. , 1979, The Journal of biological chemistry.

[46]  P. Srere,et al.  Structure of ATP citrate lyase from rat liver. Physicochemical studies and proteolytic modification. , 1976, The Journal of biological chemistry.

[47]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[48]  H. Inoue,et al.  Role of ATP in the ATP citrate lyase reaction. , 1967, Biochemical and biophysical research communications.

[49]  H. Matthews,et al.  Identification of phosphohistidine in proteins and purification of protein-histidine kinases. , 1991, Methods in enzymology.

[50]  S. Roseman,et al.  The bacterial phosphoenolpyruvate: glycose phosphotransferase system. , 1990, Annual review of biochemistry.

[51]  J. Overmeyer,et al.  Prevalence of nucleoside diphosphate kinase autophosphorylation in human colon carcinoma versus normal colon homogenates , 1989, Molecular carcinogenesis.

[52]  R. Smith,et al.  Techniques in the detection and characterization of phosphoramidate-containing proteins. , 1984, Methods in enzymology.

[53]  T. Martensen.  Chemical properties, isolation, and analysis of O-phosphates in proteins. , 1984, Methods in enzymology.

[54]  W. A. Bridger.  Contribution of subunit interactions to the effectiveness of catalysis by succinyl coenzyme A synthetase. , 1984, Current topics in cellular regulation.