• 1
    Sciacca, L., Vigneri, R., Tumminia, A., Frasca, F., Squatrito, S., et al. Clinical and molecular mechanisms favoring cancer initiation and progression in diabetic patients. Nutr. Metab. Cardiovasc. Dis., Sep:23(9):808–815.
  • 2
    Palomer, X., Salvado, L., Barroso, E., and Vazquez-Carrera, M. An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy. Int. J. Cardiol., Aug 6. pii:S0167-5273(13)01361-2.
  • 3
    Van de Voorde, J., Pauwels, B., Boydens, C., and Decaluwe, K. Adipocytokines in relation to cardiovascular disease. Metabolism, Jul 15.pii:S0026-0495(13)00184-4.
  • 4
    Gillies, R. J., Robey, I., and Gatenby, R. A. (2008) Causes and consequences of increased glucose metabolism of cancers. J. Nucl. Med. 49 Suppl 2, 24S42S.
  • 5
    Zhu, H., Klemic, J. F., Chang, S., Bertone, P., Casamayor, A., et al. (2000) Analysis of yeast protein kinases using protein chips. Nat. Genet. 26, 283289.
  • 6
    Caenepeel, S., Charydczak, G., Sudarsanam, S., Hunter, T., and Manning, G. (2004) The mouse kinome: discovery and comparative genomics of all mouse protein kinases. Proc. Natl. Acad. Sci. USA 101, 1170711712.
  • 7
    Manning, G., Whyte, D. B., Martinez, R., Hunter, T., and Sudarsanam, S. (2002) The protein kinase complement of the human genome. Science 298, 19121934.
  • 8
    Cohen, P. (2000) The regulation of protein function by multisite phosphorylation–a 25 year update. Trends Biochem. Sci. 25, 596601.
  • 9
    Melnikova, I., and Golden, J. (2004) Targeting protein kinases. Nat. Rev. Drug Discov. 3, 993994.
  • 10
    Rutter, J., Michnoff, C. H., Harper, S. M., Gardner, K. H., and McKnight, S. L. (2001) PAS kinase: an evolutionarily conserved PAS domain-regulated serine/threonine kinase. Proc. Natl. Acad. Sci. USA 98, 89918996.
  • 11
    Hofer, T., Spielmann, P., Stengel, P., Stier, B., Katschinski, D. M., et al. (2001) Mammalian PASKIN, a PAS-serine/threonine kinase related to bacterial oxygen sensors. Biochem. Biophys. Res. Commun. 288, 757764.
  • 12
    Byrne, K. P., and Wolfe, K. H. (2007) Consistent patterns of rate asymmetry and gene loss indicate widespread neofunctionalization of yeast genes after whole-genome duplication. Genetics 175, 13411350.
  • 13
    Conant, G. C., and Wolfe, K. H. (2007) Increased glycolytic flux as an outcome of whole-genome duplication in yeast. Mol. Syst. Biol. 3, 129.
  • 14
    Grassi, L., Fusco, D., Sellerio, A., Cora, D., Bassetti, B., et al. (2010) Identity and divergence of protein domain architectures after the yeast whole-genome duplication event. Mol. Bio. Syst. 6, 23052315.
  • 15
    Maclean, C. J., and Greig, D. (2011) Reciprocal gene loss following experimental whole-genome duplication causes reproductive isolation in yeast. Evolution 65, 932945.
  • 16
    Sugino, R. P., and Innan, H. (2005) Estimating the time to the whole-genome duplication and the duration of concerted evolution via gene conversion in yeast. Genetics 171, 6369.
  • 17
    Henry, J. T., and Crosson, S. (2011) Ligand-binding PAS domains in a genomic, cellular, and structural context. Annu. Rev. Microbiol. 65, 261286.
  • 18
    Taylor, B. L., and Zhulin, I. B. (1999) PAS domains: internal sensors of oxygen, redox potential, and light. Microbiol. Mol. Biol. Rev. 63, 479506.
  • 19
    Amezcua, C. A., Harper, S. M., Rutter, J., and Gardner, K. H. (2002) Structure and interactions of PAS kinase N-terminal PAS domain: model for intramolecular kinase regulation. Structure 10, 13491361.
  • 20
    Kikani, C. K., Antonysamy, S. A., Bonanno, J. B., Romero, R., Zhang, F. F., et al. (2010) Structural bases of PAS domain-regulated kinase (PASK) activation in the absence of activation loop phosphorylation. J. Biol. Chem. 285, 4103441043.
  • 21
    Johnson, L. N., Noble, M. E., and Owen, D. J. (1996) Active and inactive protein kinases: structural basis for regulation. Cell 85, 149158.
  • 22
    Grose, J. H., Smith, T. L., Sabic, H., and Rutter, J. (2007) Yeast PAS kinase coordinates glucose partitioning in response to metabolic and cell integrity signaling. EMBO J. 26, 48244830.
  • 23
    da Silva Xavier, G., Rutter, J., and Rutter, G. A. (2004) Involvement of Per-Arnt-Sim (PAS) kinase in the stimulation of preproinsulin and pancreatic duodenum homeobox 1 gene expression by glucose. Proc. Natl. Acad. Sci. USA 101, 83198324.
  • 24
    Hurtado-Carneiro, V., Roncero, I., Blazquez, E., Alvarez, E., and Sanz, C. PAS kinase as a nutrient sensor in neuroblastoma and hypothalamic cells required for the normal expression and activity of other cellular nutrient and energy sensors. Mol. Neurobiol. in press.
  • 25
    da Silva Xavier, G., Farhan, H., Kim, H., Caxaria, S., Johnson, P., et al. (2011) Per-arnt-sim (PAS) domain-containing protein kinase is downregulated in human islets in type 2 diabetes and regulates glucagon secretion. Diabetologia 54, 819827.
  • 26
    Katschinski, D. M., Marti, H. H., Wagner, K. F., Shibata, J., Eckhardt, K., et al. (2003) Targeted disruption of the mouse PAS domain serine/threonine kinase PASKIN. Mol. Cell. Biol. 23, 67806789.
  • 27
    Schlafli, P., Troger, J., Eckhardt, K., Borter, E., Spielmann, P., et al. (2011) Substrate preference and phosphatidylinositol monophosphate inhibition of the catalytic domain of the Per-Arnt-Sim domain kinase PASKIN. FEBS J. 278, 17571768.
  • 28
    Semplici, F., Vaxillaire, M., Fogarty, S., Semache, M., Bonnefond, A., et al. (2011) Human mutation within Per-Arnt-Sim (PAS) domain-containing protein kinase (PASK) causes basal insulin hypersecretion. J. Biol. Chem. 286, 4400544014.
  • 29
    An, R., da Silva Xavier, G., Hao, H. X., Semplici, F., Rutter, J., et al. (2006) Regulation by Per-Arnt-Sim (PAS) kinase of pancreatic duodenal homeobox-1 nuclear import in pancreatic beta-cells. Biochem. Soc. Trans. 34(Pt 5), 791793.
  • 30
    Hao, H. X., Cardon, C. M., Swiatek, W., Cooksey, R. C., Smith, T. L., et al. (2007) PAS kinase is required for normal cellular energy balance. Proc. Natl. Acad. Sci. USA 104, 1546615471.
  • 31
    Soliz, J., Soulage, C., Borter, E., van Patot, M. T., and Gassmann, M. (2008) Ventilatory responses to acute and chronic hypoxia are altered in female but not male Paskin-deficient mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 295, R649658.
  • 32
    Krebs, H. A. (1972) The Pasteur effect and the relations between respiration and fermentation. Essays Biochem. 8, 134.
  • 33
    Racker, E., and Wu, R. (1958) Limiting factors in glycolysis of ascites tumour cells and the pasteur effect. Regl. Cell Metab. 205229.
  • 34
    Wu, R. (1959) Regulatory mechanisms in carbohydrate metabolism. V. Limiting factors of glycolysis in HeLa cells. J. Biol. Chem. 234, 28062810.
  • 35
    Boucher, M. J., Selander, L., Carlsson, L., and Edlund, H. (2006) Phosphorylation marks IPF1/PDX1 protein for degradation by glycogen synthase kinase 3-dependent mechanisms. J. Biol. Chem. 281, 63956403.
  • 36
    Jonsson, J., Carlsson, L., Edlund, T., and Edlund, H. (1994) Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 371, 606609.
  • 37
    Rutter, J., Probst, B. L., and McKnight, S. L. (2002) Coordinate regulation of sugar flux and translation by PAS kinase. Cell 111, 1728.
  • 38
    Wilson, W. A., Skurat, A. V., Probst, B., de Paoli-Roach, A., Roach, P. J., et al. (2005) Control of mammalian glycogen synthase by PAS kinase. Proc. Natl. Acad. Sci. USA 102, 1659616601.
  • 39
    Smith, T. L., and Rutter, J. (2007) Regulation of glucose partitioning by PAS kinase and Ugp1 phosphorylation. Mol. Cell 26, 491499.
  • 40
    Eckhardt, K., Troger, J., Reissmann, J., Katschinski, D. M., Wagner, K. F., et al. (2007) Male germ cell expression of the PAS domain kinase PASKIN and its novel target eukaryotic translation elongation factor eEF1A1. Cell. Physiol. Biochem. 20, 227240.
  • 41
    Brandon, L., Probst, S. X., Leeju Wu, Carolyn, H., Michnoff, et al. Two Distinct High Throughput Screens of PAS Kinase Yield Convergent Insight to Enzyme Function. Available at:
  • 42
    Cardon, C. M., Beck, T., Hall, and M.N., Rutter, J. (2012) PAS kinase promotes cell survival and growth through activation of Rho1. Sci. Signal. 5, ra9.
  • 43
    Schmidt, A., Bickle, M., Beck, T., and Hall, M. N. (1997) The yeast phosphatidylinositol kinase homolog TOR2 activates RHO1 and RHO2 via the exchange factor ROM2. Cell 88, 531542.
  • 44
    Mihaylova, M. M., and Shaw, R. J. (2011) The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat. Cell Biol. 13, 10161023.
  • 45
    Laplante, M., and Sabatini, D. M. (2012) mTOR signaling in growth control and disease. Cell 149, 274293.
  • 46
    Quinn, B. J., Kitagawa, H., Memmott, R. M., Gills, J. J., and Dennis, P. A. Repositioning metformin for cancer prevention and treatment. Trends Endocrinol. Metab., Sep;24(9):469–80.
  • 47
    Khan, K. H., Yap, T. A., Yan, L., and Cunningham, D. (2013) Targeting the PI3K-AKT-mTOR signaling network in cancer. Chin. J. Cancer 32, 253265.
  • 48
    Grose, J. H., Sundwall, E., and Rutter, J. (2009) Regulation and function of yeast PAS kinase: a role in the maintenance of cellular integrity. Cell Cycle 8, 18241832.
  • 49
    Sievers, F., Wilm, A., Dineen, D., Gibson, T. J., Karplus, K., et al. (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539.
  • 50
    Waterhouse, A. M., Procter, J. B., Martin, D. M., Clamp, M., and Barton, G. J. (2009) Jalview Version 2–a multiple sequence alignment editor and analysis workbench. Bioinformatics 25, 11891191.