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High glucose upregulates pantothenate kinase 4 (PanK4) and thus affects M2-type pyruvate kinase (Pkm2)

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Abstract

A new Rattus norvegicus PanK gene was isolated by mRNA differential display from high concentration glucose-stimulated rat, which encodes a human PanK4-like protein with KOG2201 and KOG4584 domain. Proteins that interact with rat PanK4 were identified by the application of the yeast two-hybrid system. One of the components, Pkm2, was found to be associated with rat PanK4 and its two domains under both in vitro and in vivo conditions. Immunofluorescence staining and confocal scanning experiments showed that PanK4 could transiently co-express with Pkm2 in the cytoplasm of HeLa cell and HEK293T cell. These findings suggest that PanK4 interacts with Pkm2 and thereby may modulate the glucose metabolism through regulating the activity of Pkm2.

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Abbreviations

PanK:

Pantothenate kinase

Pkm2:

M2-type pyruvate kinase

aa:

amino acid residues

GST:

glutathione-S-transferase

PBS:

phosphate-buffered saline

HEK:

human embryonic kidney

MoAb:

monoclonal antibody

References

  1. Jackowski S Rock CO: Regulation of coenzyme A biosynthesis. J Bacteriol 148: 926–932, 1981

    PubMed  Google Scholar 

  2. Robishaw JD, Berkich DA, Neely JR: Rate-limiting step and control of coenzyme A synthesis in cardiac muscle. J. Biol Chem 257: 10967–10972, 1982

    PubMed  Google Scholar 

  3. Rock CO, Calder RB, Karim MA, Jackowski S: Pantothenate kinase regulation of the intracellular concentration of coenzyme A. J Biol Chem 275: 1377–1383, 2000

    Article  PubMed  Google Scholar 

  4. Dimroth P: The prosthetic group of citrate-lyase acyl-carrier protein. Eu. J Biochem 64: 269–281, 1976

    Article  Google Scholar 

  5. Siegmund KD, Plattner HJ, Diekmann H: Purification of ferrichrome synthetase from Aspergillus quadricinctus and characterisation as a phosphopantetheine containing multienzyme complex. Biochim Biophys Acta 1076: 123–129, 1991

    PubMed  Google Scholar 

  6. Ratnakumari L, Qureshi IA, Butterworth RF: Effect of L-carnitine on cerebral and hepatic energy metabolites in congenitally hyperammonemic sparse-fur mice and its role during benzoate therapy. Metabolism 42: 1039–1046, 1993

    Article  PubMed  Google Scholar 

  7. Calder RB, Williams RS, Ramaswamy G, Rock CO, Campbell E, Unkles SE, Kinghorn JR, Jackowski S: Cloning and characterization of a eukaryotic pantothenate kinase gene (PanK) from Aspergillus nidulans. J Biol Chem 274: 2014–2020, 1999

    Article  PubMed  Google Scholar 

  8. Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ: A novel pantothenate kinase gene (PanK2) is defective in Hallervorden-Spatz syndrome. Nat Genet 28: 345–349, 2001

    Article  PubMed  Google Scholar 

  9. Johnson MA, Kuo YM, Westaway SK, Parker SM, Ching KH, Gitschier J, Hayflick SJ: Mitochondrial localization of human PanK2 and hypotheses of secondary iron accumulation in pantothenate kinase-associated neurodegeneration. Ann N Y Acad Sci 1012: 282–298, 2004

    Article  PubMed  Google Scholar 

  10. Jackowski S, Rock CO: Regulation of coenzyme A biosynthesis. J Bacteriol 148: 926–932, 1981

    PubMed  Google Scholar 

  11. Robishaw JD, Berkich D, Neely JR: Rate-limiting step and control of coenzyme A synthesis in cardiac muscle. J Biol Chem 257: 10967–10972, 1982

    PubMed  Google Scholar 

  12. Reibel DK, Wyse BW, Berkich DA, Neely JR: Regulation of coenzyme A synthesis in heart muscle: effects of diabetes and fasting. Am J Physiol 240: H606–H611, 1981

    PubMed  Google Scholar 

  13. Reibel DK, Wyse BW, Berkich DA, Palko WM, Neely JR: Effects of diabetes and fasting on pantothenic acid metabolism in rats. Am J Physiol 240: E597–E601, 1981

    PubMed  Google Scholar 

  14. Alan RS: New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell 23: 517–529, 2001

    Google Scholar 

  15. Zhu G, Chang Y, Zuo J, Dong X, Zhang M, Hu G, Fang F: Fudenine, a C-terminal truncated rat homologue of mouse prominin, is blood glucose-regulated and can up-regulate the expression of GAPDH. Biochem Biophys Res Commun 281: 951–956, 2001

    Article  PubMed  Google Scholar 

  16. Katoh K, Shibata H, Suzuki H, Nara A, Ishidoh K, Kominami E, Yoshimori T, Maki M: The ALG-2-interacting protein alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting. J Biol Chem 278: 39104–39113, 2003

    Article  PubMed  Google Scholar 

  17. Afshar K, Gonczy P, DiNardo S, Wasserman SA: Fumble encodes a pantothenate kinase homolog required for proper mitosis and meiosis in Drosophila melanogaster. Genetics 157: 1267–1276, 2001

    PubMed  Google Scholar 

  18. Heine U, Blumenthal T: Characterization of regions of the Caenorhabditis elegans X chromosome containing vitellogenin genes. J Mol Biol 188: 301–312, 1986

    Article  PubMed  Google Scholar 

  19. Ashizawa K, Willingham MC, Liang CM, Cheng SY: In vivo regulation of monomer-tetramer conversion of pyruvate kinase subtype M2 by glucose is mediated via fructose 1,6-bisphosphate. J Biol Chem 266: 16842–16846, 1991

    PubMed  Google Scholar 

  20. Garcia-Gonzalo FR, Cruz C, Munoz P, Mazurek S, Eigenbrodt E, Ventura F, Bartrons R, Rosa JL: Interaction between HERC1 and M2-type pyruvate kinase. FEBS Lett 539: 78–84, 2003

    Article  PubMed  Google Scholar 

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Li, Y., Chang, Y., Zhang, L. et al. High glucose upregulates pantothenate kinase 4 (PanK4) and thus affects M2-type pyruvate kinase (Pkm2). Mol Cell Biochem 277, 117–125 (2005). https://doi.org/10.1007/s11010-005-5535-1

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  • DOI: https://doi.org/10.1007/s11010-005-5535-1

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