The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PRKAA2  -  protein kinase, AMP-activated, alpha 2...

Homo sapiens

Synonyms: 5'-AMP-activated protein kinase catalytic subunit alpha-2, ACACA kinase, AMPK, AMPK subunit alpha-2, AMPK2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PRKAA2

  • AMPK functions as an energy sensor to provide metabolic adaptation under ATP-depleting conditions such as hypoxia and nutritional deprivation [1].
  • We further show that reactive oxygen species is involved in glucose deprivation-induced AMPK activity in DU145 human prostate carcinomas, and c-Jun amino-terminal kinase acts as an upstream component in AMPK activation cascades under these conditions [1].
  • Using HepG2 human hepatoma cells, we found that BBR inhibits cholesterol and TG synthesis in a similar manner to the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide 1-beta-ribofuranoside (AICAR) [2].
  • The two catalytic AMPK alpha isoforms (AMPKalpha1, AMPKalpha2) were investigated with respect to their expression, cellular distribution, and contribution to VEGF expression under hypoxic stress in human U373 glioblastoma cells [3].
  • Increased alpha2 subunit-associated AMPK activity and PRKAG2 cardiomyopathy [4].

Psychiatry related information on PRKAA2

  • Accompanying this is a decrease in AMPK phosphorylation, reversible upon nicotinic acid treatment, indicating that fatty acids may modulate this kinase's activity after the metabolic challenges posed by food deprivation [5].
  • These data indicate that hypothalamic AMPK is an important signaling molecule that integrates nutritional and hormonal signals and modulates feeding behavior and energy metabolism [6].
  • Present data demonstrate for the first time that the activation of AMPK, in states of low cellular energy charge (such as under high levels of 5'-AMP) or other signals, could be a factor contributing to reduce the host defense mechanisms [7].

High impact information on PRKAA2

  • The role of the various lipid-binding proteins in transmembrane and cytosolic transport of lipids is considered as well as regulation of lipid entry into the mitochondria, focusing on the putative role of AMP-activated protein kinase (AMPK), acetyl CoA carboxylase (ACC), and carnitine during exercise [8].
  • GSK3 inhibits the mTOR pathway by phosphorylating TSC2 in a manner dependent on AMPK-priming phosphorylation [9].
  • TSC2 Integrates Wnt and Energy Signals via a Coordinated Phosphorylation by AMPK and GSK3 to Regulate Cell Growth [9].
  • New evidence suggests that leptin and other anorexigenic agents reduce appetite by inactivating hypothalamic AMP-activated protein kinase (AMPK), thereby increasing malonyl CoA levels [10].
  • Furthermore, TSC2 and its phosphorylation by AMPK protect cells from energy deprivation-induced apoptosis [11].

Chemical compound and disease context of PRKAA2


Biological context of PRKAA2

  • Haplotype structures and large-scale association testing of the 5' AMP-activated protein kinase genes PRKAA2, PRKAB1, and PRKAB1 with type 2 diabetes [17].
  • METHOD: We examined association of 5 tagging SNPs (tSNPs) in the PRKAA2 gene with serum lipids in 2777 normal Caucasian females (mean age 47.4+/-12.5 years) [18].
  • Expression of a constitutively active form of AMPK mimics the PB induction of CYP2B6 and CYP2B1 gene expression [19].
  • We therefore set out to test for the association of common variants in the genes that encode three selected AMPK subunits with type 2 diabetes and related phenotypes [17].
  • Knockdown of AMPK using RNA interference and application of the AMPK inhibitor, Compound C, supported this conclusion [20].

Anatomical context of PRKAA2


Associations of PRKAA2 with chemical compounds

  • AMP-kinase alpha2 subunit gene PRKAA2 variants are associated with total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol in normal women [18].
  • In the present study, we examined the mechanisms of VEGF gene expression induced by glucose deprivation in cancer cells, a role of AMP-activated protein kinase (AMPK) in the process, and the signal transduction pathway [1].
  • AMP-activated protein kinase (AMPK) is a key molecular regulator of cellular metabolism, and its activity is induced by both metformin and thiazolidinedione antidiabetic medications [17].
  • Both leptin and CNTF reduced AMPK activity and acetyl-coenzyme A carboxylase phosphorylation in the ARC and PVN of control-fed mice [25].
  • 5'-AMP-activated protein kinase (AMPK) acts as a major regulator of cellular ATP levels and protects cells against stresses that cause ATP depletion [26].
  • The inhibition of AMPK and p38 MAPK blocked retinoic acid-induced glucose uptake [27].

Enzymatic interactions of PRKAA2

  • In conclusion, the present study suggests that AMPK phosphorylates HSL on Ser565 in human skeletal muscle during exercise with reduced muscle glycogen [28].
  • In the thigh muscle, the alpha AMPK subunits became progressively more phosphorylated on Thr(172) during exercise eliciting a parallel increase in alpha2 but not alpha1 AMPK activity [29].

Regulatory relationships of PRKAA2

  • In the current study, we tested the capacity of 5'AMP-activated protein kinase (AMPK) to suppress beta-adrenergic stimulation of HSL activity [30].
  • It has been reported recently that AMPK (AMP-activated protein kinase) is involved in phenobarbital-mediated CYP2B induction in a particular culture system [31].
  • Taken together, these results suggest that VEGF and S1P differentially regulate AMPK and establish a central role for an agonist-modulated AMPK --> Rac1 --> Akt axis in the control of eNOS in endothelial cells [32].
  • Activated AMPK promotes inhibition of mammalian target of rapamycin (mTOR) kinase, which could be deleterious to the viral infection [33].

Other interactions of PRKAA2

  • Furthermore, IL-6 rapidly and markedly increased AMP-activated protein kinase (AMPK) [22].
  • Several nominal associations of variants in PRKAA2 and PRKAB1 with BMI appear to be consistent with statistical noise [17].
  • To confirm the apparent effect of AMPK on HSL activity, we performed experiments in muscle cell culture [30].
  • Dissociation of AMPK activity and ACCbeta phosphorylation in human muscle during prolonged exercise [29].
  • Activation of AMPK has been associated with enhanced expression of key metabolic proteins such as GLUT-4, hexokinase II (HKII), and mitochondrial enzymes, similar to exercise [34].

Analytical, diagnostic and therapeutic context of PRKAA2


  1. Glucose deprivation increases mRNA stability of vascular endothelial growth factor through activation of AMP-activated protein kinase in DU145 prostate carcinoma. Yun, H., Lee, M., Kim, S.S., Ha, J. J. Biol. Chem. (2005) [Pubmed]
  2. Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine. Brusq, J.M., Ancellin, N., Grondin, P., Guillard, R., Martin, S., Saintillan, Y., Issandou, M. J. Lipid Res. (2006) [Pubmed]
  3. AMP-dependent protein kinase alpha 2 isoform promotes hypoxia-induced VEGF expression in human glioblastoma. Neurath, K.M., Keough, M.P., Mikkelsen, T., Claffey, K.P. Glia (2006) [Pubmed]
  4. Increased alpha2 subunit-associated AMPK activity and PRKAG2 cardiomyopathy. Ahmad, F., Arad, M., Musi, N., He, H., Wolf, C., Branco, D., Perez-Atayde, A.R., Stapleton, D., Bali, D., Xing, Y., Tian, R., Goodyear, L.J., Berul, C.I., Ingwall, J.S., Seidman, C.E., Seidman, J.G. Circulation (2005) [Pubmed]
  5. Sequential changes in the signal transduction responses of skeletal muscle following food deprivation. de Lange, P., Farina, P., Moreno, M., Ragni, M., Lombardi, A., Silvestri, E., Burrone, L., Lanni, A., Goglia, F. FASEB J. (2006) [Pubmed]
  6. Role of hypothalamic 5'-AMP-activated protein kinase in the regulation of food intake and energy homeostasis. Kim, M.S., Lee, K.U. J. Mol. Med. (2005) [Pubmed]
  7. Stimulators of AMP-activated protein kinase inhibit the respiratory burst in human neutrophils. Alba, G., El Bekay, R., Alvarez-Maqueda, M., Chacón, P., Vega, A., Monteseirín, J., Santa María, C., Pintado, E., Bedoya, F.J., Bartrons, R., Sobrino, F. FEBS Lett. (2004) [Pubmed]
  8. Skeletal muscle lipid metabolism in exercise and insulin resistance. Kiens, B. Physiol. Rev. (2006) [Pubmed]
  9. TSC2 Integrates Wnt and Energy Signals via a Coordinated Phosphorylation by AMPK and GSK3 to Regulate Cell Growth. Inoki, K., Ouyang, H., Zhu, T., Lindvall, C., Wang, Y., Zhang, X., Yang, Q., Bennett, C., Harada, Y., Stankunas, K., Wang, C.Y., He, X., Macdougald, O.A., You, M., Williams, B.O., Guan, K.L. Cell (2006) [Pubmed]
  10. The hyperleptinemia of obesity-regulator of caloric surpluses. Unger, R.H. Cell (2004) [Pubmed]
  11. TSC2 mediates cellular energy response to control cell growth and survival. Inoki, K., Zhu, T., Guan, K.L. Cell (2003) [Pubmed]
  12. AMP-activated protein kinase is required for the lipid-lowering effect of metformin in insulin-resistant human HepG2 cells. Zang, M., Zuccollo, A., Hou, X., Nagata, D., Walsh, K., Herscovitz, H., Brecher, P., Ruderman, N.B., Cohen, R.A. J. Biol. Chem. (2004) [Pubmed]
  13. AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues. Xue, B., Kahn, B.B. J. Physiol. (Lond.) (2006) [Pubmed]
  14. Critical role of 5'-AMP-activated protein kinase in the stimulation of glucose transport in response to inhibition of oxidative phosphorylation. Jing, M., Ismail-Beigi, F. Am. J. Physiol., Cell Physiol. (2007) [Pubmed]
  15. Effects of adenosine on myocardial glucose and palmitate metabolism after transient ischemia: role of 5'-AMP-activated protein kinase. Jaswal, J.S., Gandhi, M., Finegan, B.A., Dyck, J.R., Clanachan, A.S. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  16. Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway. Hwang, J.T., Ha, J., Park, I.J., Lee, S.K., Baik, H.W., Kim, Y.M., Park, O.J. Cancer Lett. (2007) [Pubmed]
  17. Haplotype structures and large-scale association testing of the 5' AMP-activated protein kinase genes PRKAA2, PRKAB1, and PRKAB1 with type 2 diabetes. Sun, M.W., Lee, J.Y., de Bakker, P.I., Burtt, N.P., Almgren, P., Råstam, L., Tuomi, T., Gaudet, D., Daly, M.J., Hirschhorn, J.N., Altshuler, D., Groop, L., Florez, J.C. Diabetes (2006) [Pubmed]
  18. AMP-kinase alpha2 subunit gene PRKAA2 variants are associated with total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol in normal women. Spencer-Jones, N.J., Ge, D., Snieder, H., Perks, U., Swaminathan, R., Spector, T.D., Carter, N.D., O'Dell, S.D. J. Med. Genet. (2006) [Pubmed]
  19. AMP-activated protein kinase mediates phenobarbital induction of CYP2B gene expression in hepatocytes and a newly derived human hepatoma cell line. Rencurel, F., Stenhouse, A., Hawley, S.A., Friedberg, T., Hardie, D.G., Sutherland, C., Wolf, C.R. J. Biol. Chem. (2005) [Pubmed]
  20. Activation of Lipoprotein Lipase by Glucose-dependent Insulinotropic Polypeptide in Adipocytes: A ROLE FOR A PROTEIN KINASE B, LKB1, AND AMP-ACTIVATED PROTEIN KINASE CASCADE. Kim, S.J., Nian, C., McIntosh, C.H. J. Biol. Chem. (2007) [Pubmed]
  21. Adenosine 5'-Monophosphate Kinase-Activated Protein Kinase (PRKA) Activators Delay Meiotic Resumption in Porcine Oocytes. Mayes, M.A., Laforest, M.F., Guillemette, C., Gilchrist, R.B., Richard, F.J. Biol. Reprod. (2007) [Pubmed]
  22. Interleukin-6 Increases Insulin-Stimulated Glucose Disposal in Humans and Glucose Uptake and Fatty Acid Oxidation In Vitro via AMP-Activated Protein Kinase. Carey, A.L., Steinberg, G.R., Macaulay, S.L., Thomas, W.G., Holmes, A.G., Ramm, G., Prelovsek, O., Hohnen-Behrens, C., Watt, M.J., James, D.E., Kemp, B.E., Pedersen, B.K., Febbraio, M.A. Diabetes (2006) [Pubmed]
  23. Regulation of channel gating by AMP-activated protein kinase modulates cystic fibrosis transmembrane conductance regulator activity in lung submucosal cells. Hallows, K.R., McCane, J.E., Kemp, B.E., Witters, L.A., Foskett, J.K. J. Biol. Chem. (2003) [Pubmed]
  24. Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398. Browne, G.J., Finn, S.G., Proud, C.G. J. Biol. Chem. (2004) [Pubmed]
  25. Ciliary neurotrophic factor suppresses hypothalamic AMP-kinase signaling in leptin-resistant obese mice. Steinberg, G.R., Watt, M.J., Fam, B.C., Proietto, J., Andrikopoulos, S., Allen, A.M., Febbraio, M.A., Kemp, B.E. Endocrinology (2006) [Pubmed]
  26. Molecular cloning, genomic organization, and mapping of PRKAG2, a heart abundant gamma2 subunit of 5'-AMP-activated protein kinase, to human chromosome 7q36. Lang, T., Yu, L., Tu, Q., Jiang, J., Chen, Z., Xin, Y., Liu, G., Zhao, S. Genomics (2000) [Pubmed]
  27. Retinoic acid leads to cytoskeletal rearrangement through AMPK-Rac1 and stimulates glucose uptake through AMPK-p38 MAPK in skeletal muscle cells. Lee, Y.M., Lee, J.O., Jung, J.H., Kim, J.H., Park, S.H., Park, J.M., Kim, E.K., Suh, P.G., Kim, H.S. J. Biol. Chem. (2008) [Pubmed]
  28. Regulation of hormone-sensitive lipase activity and Ser563 and Ser565 phosphorylation in human skeletal muscle during exercise. Roepstorff, C., Vistisen, B., Donsmark, M., Nielsen, J.N., Galbo, H., Green, K.A., Hardie, D.G., Wojtaszewski, J.F., Richter, E.A., Kiens, B. J. Physiol. (Lond.) (2004) [Pubmed]
  29. Dissociation of AMPK activity and ACCbeta phosphorylation in human muscle during prolonged exercise. Wojtaszewski, J.F., Mourtzakis, M., Hillig, T., Saltin, B., Pilegaard, H. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  30. Beta-adrenergic stimulation of skeletal muscle HSL can be overridden by AMPK signaling. Watt, M.J., Steinberg, G.R., Chan, S., Garnham, A., Kemp, B.E., Febbraio, M.A. FASEB J. (2004) [Pubmed]
  31. A physiological role of AMP-activated protein kinase in phenobarbital-mediated constitutive androstane receptor activation and CYP2B induction. Shindo, S., Numazawa, S., Yoshida, T. Biochem. J. (2007) [Pubmed]
  32. Agonist-modulated regulation of AMP-activated protein kinase (AMPK) in endothelial cells. Evidence for an AMPK -> Rac1 -> Akt -> endothelial nitric-oxide synthase pathway. Levine, Y.C., Li, G.K., Michel, T. J. Biol. Chem. (2007) [Pubmed]
  33. AMPK-mediated inhibition of mTOR kinase is circumvented during immediate-early times of human cytomegalovirus infection. Kudchodkar, S.B., Del Prete, G.Q., Maguire, T.G., Alwine, J.C. J. Virol. (2007) [Pubmed]
  34. Exercise increases nuclear AMPK alpha2 in human skeletal muscle. McGee, S.L., Howlett, K.F., Starkie, R.L., Cameron-Smith, D., Kemp, B.E., Hargreaves, M. Diabetes (2003) [Pubmed]
  35. Characterization and chromosomal localization of the human homologue of a rat AMP-activated protein kinase-encoding gene: a major regulator of lipid metabolism in mammals. Aguan, K., Scott, J., See, C.G., Sarkar, N.H. Gene (1994) [Pubmed]
  36. The bovine 5' AMPK gene family: mapping and single nucleotide polymorphism detection. McKay, S.D., White, S.N., Kata, S.R., Loan, R., Womack, J.E. Mamm. Genome (2003) [Pubmed]
  37. Molecular cloning, expression and chromosomal localisation of human AMP-activated protein kinase. Beri, R.K., Marley, A.E., See, C.G., Sopwith, W.F., Aguan, K., Carling, D., Scott, J., Carey, F. FEBS Lett. (1994) [Pubmed]
WikiGenes - Universities