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Gene Review

PCK2  -  phosphoenolpyruvate carboxykinase 2...

Homo sapiens

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Disease relevance of PCK2

  • A significant (p = 0.02) reduction in expression of phosphoenolpyruvate carboxykinase (PCK2) was observed following siRNA inhibition of INSIG1 in human Huh7 hepatoma cells [1].
  • Phosphoenolpyruvate carboxylase from pennywort (Umbilicus rupestris). Changes in properties after exposure to water stress [2].
  • Purification and characterization of the phosphoenolpyruvate carboxylase from the facultative chemolithotroph Thiobacillus novellus (ATCC 8093) [3].
  • Phosphoenolpyruvate carboxylase (EC (PEP-C) was purified approximately 770-fold from the mollicute Acholeplasma laidlawii B-PG9 [4].
  • Transgenic bean plants were generated which express a Corynebacterium glutamicum phosphoenolpyruvate carboxylase (PEPC) in a seed-specific manner [5].

High impact information on PCK2

  • Phosphoenolpyruvate carboxykinase (GTP) (EC (PEPCK) is a key enzyme in the synthesis of glucose in the liver and kidney and of glyceride-glycerol in white adipose tissue and the small intestine [6].
  • Glucocorticoids and adenosine 3',5'-monophosphate (cAMP) increase PEPCK gene transcription and gluconeogenesis, whereas insulin has the opposite effect [7].
  • Glucocorticoid and cAMP response elements have been located in the PEPCK gene and now a 15-base pair insulin-responsive sequence (IRS) is described [7].
  • We have followed, in situ, the accumulation of malic enzyme (ME), phosphoenolpyruvate carboxylase (PEPCase), and ribulose bisphosphate carboxylase (RuBPCase) mRNAs in developing leaves of both normal and mutant argentia (ar) maize [8].
  • Relatively little is known about how mRNA stability is regulated in general, but it is clear that PEPCK mRNA is stabilized by agents that increase the rate of transcription of the gene [9].

Chemical compound and disease context of PCK2


Biological context of PCK2

  • The aim of this study was to identify genetic polymorphisms in potential candidate genes for type 2 diabetes by sequencing all exons in the PCK genes (PCK1 and PCK2), and examining the association with type 2 diabetes and diabetic phenotypes in a Korean population (775 type 2 diabetic patients and 316 normal control subjects) [14].
  • PCK2 is located 1 kbp upstream and is the essential element of an adipocyte specific enhancer [15].
  • Phosphoenolpyruvate carboxylase (PEPC), a key enzyme of primary metabolism of higher plants, is regulated by reversible phosphorylation, which is catalyzed by PEPC kinase (PPCK) [16].
  • Potato PEPC was mutated either by modifications of the N-terminal phosphorylation site or by an exchange of an internal cDNA segment for the homologous sequence of PEPC from the C4 plant Flaveria trinervia [17].
  • Phosphoenolpyruvate carboxykinase (PEPCK) is one of the key regulatory enzymes in gluconeogenesis [18].

Anatomical context of PCK2

  • Marker proteins for epithelial and bile duct cells, cytokeratin (CK) 18 and 19, and liver-specific proteins, like phosphoenolpyruvate carboxykinase-2 (PCK2) and serum proteins, were expressed [19].
  • A clear increase in PEPC was observed in the scutellar epithelium of grains 24 h after imbibition [20].
  • In human liver, PEPCK is about equally distributed in both cytosol (PEPCK-1) and mitochondria (PEPCK-2) [18].
  • The photosynthetic isoform of PEPC in the cytosol of mesophyll cells in Kranz-type C(4) photosynthesis has distinctive kinetic and regulatory properties [21].
  • Regulatory phosphorylation of phosphoenolpyruvate carboxylase in protoplasts from Sorghum mesophyll cells and the role of pH and Ca2+ as possible components of the light-transduction pathway [22].

Associations of PCK2 with chemical compounds

  • Phosphoenolpyruvate carboxylase (PEPC) is believed to play an important role in producing malate as a substrate for fatty acid synthesis by leucoplasts of the developing castor oilseed (COS) endosperm [23].
  • These observations indicate that the regulation systems which direct cell-specific and light-inducible expression of pepc and rbcS in C4 plants are also present in C3 plants [24].
  • Nevertheless, expression of endogenous pepc in C3 plants is very low in C3 mesophyll cells, and the cell specificity of rbcS expression in C3 plants differs from that in C4 plants [24].
  • Phosphoenolpyruvate carboxylase (PEPC) plays a crucial role in the assimilation of CO2 during symbiotic N2 fixation in legume root nodules [25].
  • Phosphoenolpyruvate carboxylase (PEPC) activity and corresponding mRNA levels were investigated in developing and germinating wheat (Triticum aestivum) grains [20].

Other interactions of PCK2

  • Moreover, electrophoretic mobility shift experiments indicated that, unlike PCK2, PCK1 is not selective for PPARgamma/RXR binding [26].
  • Using gel shift experiments, we show that this effect is likely to involve the human PCK2 (hPCK2) element, which binds a protein complex that contains PPARgamma and RXRalpha [27].
  • Using a specially designed isokinetic-isopycnic sucrose density gradient centrifugation method, the distribution of hexokinase activity correlated with that of the mitochondrial marker (cytochrome oxidase) and not with that of the chloroplast membrane marker ( chlorophyll ) or that of the cytosol marker (phosphoenolpyruvate carboxylase) [28].

Analytical, diagnostic and therapeutic context of PCK2

  • Two kinetically distinct isoforms of COS PEPC were resolved by gel filtration chromatography and purified [23].
  • Western-blot experiments detected two main PEPC polypeptides with apparent molecular masses of 108 and 103 kD [20].
  • Immunoblotting studies established that the 100 kDa subunit did not arise via proteolysis of the 103 kDa subunit after tissue extraction, and that the subunit composition of banana PEPC remains uniform throughout the ripening process [29].
  • Southern blot analysis of spruce genomic DNA under low-stringency conditions using the PEPC cDNA as a hybridization probe showed a complex hybridization pattern, indicating the presence of additional PEPC-related sequences in the genome of the spruce [30].
  • In order to mimic regulatory phosphorylation of the Ser-15 of maize C4-form phosphoenolpyruvate carboxylase (PEPC), we replaced Ser-15 and Lys-12 with Asp (S15D) and Asn (K12N), respectively, by site-directed mutagenesis [31].


  1. Human evidence for the involvement of insulin-induced gene 1 in the regulation of plasma glucose concentration. Krapivner, S., Chernogubova, E., Ericsson, M., Ahlbeck-Glader, C., Hamsten, A., van 't Hooft, F.M. Diabetologia (2007) [Pubmed]
  2. Phosphoenolpyruvate carboxylase from pennywort (Umbilicus rupestris). Changes in properties after exposure to water stress. Daniel, P.P., Bryant, J.A., Woodward, F.I. Biochem. J. (1984) [Pubmed]
  3. Purification and characterization of the phosphoenolpyruvate carboxylase from the facultative chemolithotroph Thiobacillus novellus (ATCC 8093). Charles, A.M., Sykora, Y. Antonie Van Leeuwenhoek (1992) [Pubmed]
  4. The anaplerotic phosphoenolpyruvate carboxylase of the tricarboxylic acid cycle deficient Acholeplasma laidlawii B-PG9. Manolukas, J.T., Williams, M.V., Pollack, J.D. J. Gen. Microbiol. (1989) [Pubmed]
  5. Seed-specific expression of a bacterial phosphoenolpyruvate carboxylase in Vicia narbonensis increases protein content and improves carbon economy. Rolletschek, H., Borisjuk, L., Radchuk, R., Miranda, M., Heim, U., Wobus, U., Weber, H. Plant Biotechnol. J. (2004) [Pubmed]
  6. Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression. Hanson, R.W., Reshef, L. Annu. Rev. Biochem. (1997) [Pubmed]
  7. Identification of a sequence in the PEPCK gene that mediates a negative effect of insulin on transcription. O'Brien, R.M., Lucas, P.C., Forest, C.D., Magnuson, M.A., Granner, D.K. Science (1990) [Pubmed]
  8. Cellular pattern of photosynthetic gene expression in developing maize leaves. Langdale, J.A., Rothermel, B.A., Nelson, T. Genes Dev. (1988) [Pubmed]
  9. Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Pilkis, S.J., Granner, D.K. Annu. Rev. Physiol. (1992) [Pubmed]
  10. Insulin represses phosphoenolpyruvate carboxykinase gene transcription by causing the rapid disruption of an active transcription complex: a potential epigenetic effect. Hall, R.K., Wang, X.L., George, L., Koch, S.R., Granner, D.K. Mol. Endocrinol. (2007) [Pubmed]
  11. Molecular cloning of two DNA-binding proteins of maize that are structurally different but interact with the same sequence motif. Yanagisawa, S., Izui, K. J. Biol. Chem. (1993) [Pubmed]
  12. Chronic hyperglycemia enhances PEPCK gene expression and hepatocellular glucose production via elevated liver activating protein/liver inhibitory protein ratio. Shao, J., Qiao, L., Janssen, R.C., Pagliassotti, M., Friedman, J.E. Diabetes (2005) [Pubmed]
  13. Multihormonal regulation of phosphoenolpyruvate carboxykinase-chloramphenicol acetyltransferase fusion genes. Insulin's effects oppose those of cAMP and dexamethasone. Magnuson, M.A., Quinn, P.G., Granner, D.K. J. Biol. Chem. (1987) [Pubmed]
  14. Association of a polymorphism in the gene encoding phosphoenolpyruvate carboxykinase 1 with high-density lipoprotein and triglyceride levels. Shin, H.D., Park, B.L., Kim, L.H., Cheong, H.S., Kim, J.H., Cho, Y.M., Lee, H.K., Park, K.S. Diabetologia (2005) [Pubmed]
  15. Regulation of cytosolic phosphoenolpyruvate carboxykinase gene expression in adipocytes. Beale, E.G., Forest, C., Hammer, R.E. Biochimie (2003) [Pubmed]
  16. Characterization and functional analysis of phosphoenolpyruvate carboxylase kinase genes in rice. Fukayama, H., Tamai, T., Taniguchi, Y., Sullivan, S., Miyao, M., Nimmo, H.G. Plant J. (2006) [Pubmed]
  17. An engineered phosphoenolpyruvate carboxylase redirects carbon and nitrogen flow in transgenic potato plants. Rademacher, T., Häusler, R.E., Hirsch, H.J., Zhang, L., Lipka, V., Weier, D., Kreuzaler, F., Peterhänsel, C. Plant J. (2002) [Pubmed]
  18. Cloning and reporter analysis of human mitochondrial phosphoenolpyruvate carboxykinase gene promoter. Suzuki, M., Yamasaki, T., Shinohata, R., Hata, M., Nakajima, H., Kono, N. Gene (2004) [Pubmed]
  19. Serum-free, long-term cultures of human hepatocytes: maintenance of cell morphology, transcription factors, and liver-specific functions. Runge, D., Runge, D.M., Jäger, D., Lubecki, K.A., Beer Stolz, D., Karathanasis, S., Kietzmann, T., Strom, S.C., Jungermann, K., Fleig, W.E., Michalopoulos, G.K. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  20. Expression and localization of phosphoenolpyruvate carboxylase in developing and germinating wheat grains. González, M.C., Osuna, L., Echevarría, C., Vidal, J., Cejudo, F.J. Plant Physiol. (1998) [Pubmed]
  21. Species having c4 single-cell-type photosynthesis in the chenopodiaceae family evolved a photosynthetic phosphoenolpyruvate carboxylase like that of kranz-type c4 species. Lara, M.V., Chuong, S.D., Akhani, H., Andreo, C.S., Edwards, G.E. Plant Physiol. (2006) [Pubmed]
  22. Regulatory phosphorylation of phosphoenolpyruvate carboxylase in protoplasts from Sorghum mesophyll cells and the role of pH and Ca2+ as possible components of the light-transduction pathway. Pierre, J.N., Pacquit, V., Vidal, J., Gadal, P. Eur. J. Biochem. (1992) [Pubmed]
  23. Structural and kinetic properties of high and low molecular mass phosphoenolpyruvate carboxylase isoforms from the endosperm of developing castor oilseeds. Blonde, J.D., Plaxton, W.C. J. Biol. Chem. (2003) [Pubmed]
  24. The promoters of two carboxylases in a C4 plant (maize) direct cell-specific, light-regulated expression in a C3 plant (rice). Matsuoka, M., Kyozuka, J., Shimamoto, K., Kano-Murakami, Y. Plant J. (1994) [Pubmed]
  25. Analyses of phosphoenolpyruvate carboxylase gene structure and expression in alfalfa nodules. Pathirana, M.S., Samac, D.A., Roeven, R., Yoshioka, H., Vance, C.P., Gantt, J.S. Plant J. (1997) [Pubmed]
  26. Adipose expression of the phosphoenolpyruvate carboxykinase promoter requires peroxisome proliferator-activated receptor gamma and 9-cis-retinoic acid receptor binding to an adipocyte-specific enhancer in vivo. Devine, J.H., Eubank, D.W., Clouthier, D.E., Tontonoz, P., Spiegelman, B.M., Hammer, R.E., Beale, E.G. J. Biol. Chem. (1999) [Pubmed]
  27. Expression of phosphoenolpyruvate carboxykinase gene in human adipose tissue: induction by rosiglitazone and genetic analyses of the adipocyte-specific region of the promoter in type 2 diabetes. Duplus, E., Benelli, C., Reis, A.F., Fouque, F., Velho, G., Forest, C. Biochimie (2003) [Pubmed]
  28. Subcellular localization of hexokinase in pea leaves. Evidence for the predominance of a mitochondrially bound form. Cosio, E., Bustamante, E. J. Biol. Chem. (1984) [Pubmed]
  29. Purification and characterization of a novel phosphoenolpyruvate carboxylase from banana fruit. Law, R.D., Plaxton, W.C. Biochem. J. (1995) [Pubmed]
  30. Molecular characterization of a phosphoenolpyruvate carboxylase in the gymnosperm Picea abies (Norway spruce). Relle, M., Wild, A. Plant Mol. Biol. (1996) [Pubmed]
  31. Regulatory phosphorylation of plant phosphoenolpyruvate carboxylase: role of a conserved basic residue upstream of the phosphorylation site. Ueno, Y., Hata, S., Izui, K. FEBS Lett. (1997) [Pubmed]
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