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Gene Review

PRKAA1  -  protein kinase, AMP-activated, alpha 1...

Homo sapiens

Synonyms: 5'-AMP-activated protein kinase catalytic subunit alpha-1, ACACA kinase, AMPK, AMPK subunit alpha-1, AMPK1, ...
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Disease relevance of PRKAA1

  • Anoxia activates AMP-activated protein kinase (AMPK, see ), resulting in the inhibition of biosynthetic pathways to conserve ATP [1].
  • CONCLUSIONS: Taken together, our findings suggest that AMPK may play a key role in regulating the effects of ethanol on SREBP-1 activation, fatty acid metabolism, and development of alcoholic fatty liver [2].
  • In yeast, SNF1 is one of the main regulators in the shift from fermentation to aerobic metabolism; AMPK, its mammalian counterpart, is a master metabolic regulator involved in a variety of metabolic disorders such as diabetes and obesity [3].
  • Isolated neonatal cardiac myocytes infected with an adenovirus expressing constitutively active mutant forms of either Akt1 or Akt2 also suppressed AMPK phosphorylation [4].
  • Of note, substitution of HFD with regular diet causes a robust recovery of soleus AMPK and ACC phosphorylation in LepTg, with a higher rate of body weight reduction and a regain of insulin sensitivity [5].

Psychiatry related information on PRKAA1

  • 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 [6].
  • alpha 2-Adrenergic receptors modulate the release of several neurotransmitters implicated in the treatment and pathophysiology of mood and anxiety disorders [7].
  • Relationships between Alpha (8-12 Hz) activity and cognitive processes during wakefulness raise the possibility of similar relationships between Alpha and cognitive activity during sleep [8].
  • Memory performance was assessed by four tests: Alpha Span, Brown-Peterson, Hopkins Verbal Learning Test - Revised (HVLT-R), and Logical Stories [9].
  • alpha- and beta-secretase: profound changes in Alzheimer's disease [10].

High impact information on PRKAA1

  • GSK3 inhibits the mTOR pathway by phosphorylating TSC2 in a manner dependent on AMPK-priming phosphorylation [11].
  • TSC2 Integrates Wnt and Energy Signals via a Coordinated Phosphorylation by AMPK and GSK3 to Regulate Cell Growth [11].
  • Our data may provide a novel paradigm that an adipocyte-derived antidiabetic hormone, Ad, activates AMPK, thereby directly regulating glucose metabolism and insulin sensitivity in vitro and in vivo [12].
  • alpha foetoprotein and serum albumin show sequence homology [13].
  • Several promising therapeutic strategies based on modulation of AMPK, HIF and other metabolic targets have been proposed to exploit the addiction of tumor cells to increased glucose uptake and glycolysis [14].

Chemical compound and disease context of PRKAA1


Biological context of PRKAA1


Anatomical context of PRKAA1


Associations of PRKAA1 with chemical compounds

  • Mutation of the T-loop Thr phosphorylated by LKB1 to Ala prevented activation, while mutation to glutamate produced active forms of many of the AMPK-related kinases [24].
  • In our study, 5-amino-imidazolecarboxamide (AICA) riboside, a stimulator of AMP kinase, significantly inhibited glucose-mediated activation of ACC and insulin secretion from isolated beta-cells [25].
  • Exercise for 3 h increased AdipoR1/R2 mRNA expression as well as phosphorylation of AMPK and acetyl coenzyme A carboxylase in muscle, but had no effect on circulating adiponectin [26].
  • Finally, we measured these same variables in addition to protein levels of AMP kinase (AMPK), acetyl phosphorylated AMPK, coenzyme A carboxylase, phosphorylated coenzyme A carboxylase, and phosphatidylinositol 3-kinase in muscle before and after 3 h of intensive exercise in a subgroup of five subjects [26].
  • It also increased AMPK and acetyl CoA carboxylase phosphorylation (P-AMPK and P-ACC) and decreased the concentration of malonyl CoA confirming that AMPK activation had occurred [21].

Enzymatic interactions of PRKAA1

  • AMPK phosphorylates and inhibits acetyl-coenzyme A (CoA) carboxylase (ACC) and enhances GLUT-4 translocation [27].
  • Recent work has shown that the LKB1 tumour suppressor protein kinase phosphorylates and activates protein kinases belonging to the AMP activated kinase (AMPK) subfamily [28].

Regulatory relationships of PRKAA1


Other interactions of PRKAA1

  • Insulin-like Growth Factor-I Signaling Mechanisms, Type I Collagen and Alpha Smooth Muscle Actin in Human Fetal Lung Fibroblasts [32].
  • Hypoxia results in energy starvation and activation of the AMPK/TSC2/Rheb/mTOR pathway [33].
  • Inhibition of germline proliferation during C. elegans dauer development requires PTEN, LKB1 and AMPK signalling [34].
  • We identified a novel human AMP-activated protein kinase (AMPK) family member, designated ARK5, encoding 661 amino acids with an estimated molecular mass of 74 kDa [35].
  • alpha IR-3, a monoclonal antibody that interacts with the somatomedin-C receptor, inhibited the binding of somatomedin-C, but not of insulin, to human placental membranes and intact IM-9 cells. alpha IR-1, a monoclonal antibody that interacts with the insulin receptor, did not inhibit the binding of either hormone [36].

Analytical, diagnostic and therapeutic context of PRKAA1


  1. Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Horman, S., Browne, G., Krause, U., Patel, J., Vertommen, D., Bertrand, L., Lavoinne, A., Hue, L., Proud, C., Rider, M. Curr. Biol. (2002) [Pubmed]
  2. The role of AMP-activated protein kinase in the action of ethanol in the liver. You, M., Matsumoto, M., Pacold, C.M., Cho, W.K., Crabb, D.W. Gastroenterology (2004) [Pubmed]
  3. SNF1/AMPK/SnRK1 kinases, global regulators at the heart of energy control? Polge, C., Thomas, M. Trends Plant Sci. (2007) [Pubmed]
  4. Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart. Kovacic, S., Soltys, C.L., Barr, A.J., Shiojima, I., Walsh, K., Dyck, J.R. J. Biol. Chem. (2003) [Pubmed]
  5. Skeletal muscle AMP-activated protein kinase phosphorylation parallels metabolic phenotype in leptin transgenic mice under dietary modification. Tanaka, T., Hidaka, S., Masuzaki, H., Yasue, S., Minokoshi, Y., Ebihara, K., Chusho, H., Ogawa, Y., Toyoda, T., Sato, K., Miyanaga, F., Fujimoto, M., Tomita, T., Kusakabe, T., Kobayashi, N., Tanioka, H., Hayashi, T., Hosoda, K., Yoshimatsu, H., Sakata, T., Nakao, K. Diabetes (2005) [Pubmed]
  6. 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]
  7. Gender differences in brain metabolic and plasma catecholamine responses to alpha 2-adrenoceptor blockade. Schmidt, M.E., Matochik, J.A., Goldstein, D.S., Schouten, J.L., Zametkin, A.J., Potter, W.Z. Neuropsychopharmacology (1997) [Pubmed]
  8. Reduced Alpha power associated with the recall of mentation from Stage 2 and Stage REM sleep. Esposito, M.J., Nielsen, T.A., Paquette, T. Psychophysiology. (2004) [Pubmed]
  9. Cognitive rehabilitation in the elderly: Effects on memory. Craik, F.I., Winocur, G., Palmer, H., Binns, M.A., Edwards, M., Bridges, K., Glazer, P., Chavannes, R., Stuss, D.T. Journal of the International Neuropsychological Society : JINS (2007) [Pubmed]
  10. alpha- and beta-secretase: profound changes in Alzheimer's disease. Tyler, S.J., Dawbarn, D., Wilcock, G.K., Allen, S.J. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  11. 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]
  12. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., Eto, K., Akanuma, Y., Froguel, P., Foufelle, F., Ferre, P., Carling, D., Kimura, S., Nagai, R., Kahn, B.B., Kadowaki, T. Nat. Med. (2002) [Pubmed]
  13. alpha foetoprotein and serum albumin show sequence homology. Ruoslahti, E., Terry, W.D. Nature (1976) [Pubmed]
  14. Glucose metabolism and cancer. Shaw, R.J. Curr. Opin. Cell Biol. (2006) [Pubmed]
  15. AMP-activated protein kinase--development of the energy sensor concept. Hardie, D.G., Hawley, S.A., Scott, J.W. J. Physiol. (Lond.) (2006) [Pubmed]
  16. 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]
  17. 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]
  18. Malonyl CoA control of fatty acid oxidation in the ischemic heart. Dyck, J.R., Lopaschuk, G.D. J. Mol. Cell. Cardiol. (2002) [Pubmed]
  19. Direct activation of AMP-activated protein kinase stimulates nitric-oxide synthesis in human aortic endothelial cells. Morrow, V.A., Foufelle, F., Connell, J.M., Petrie, J.R., Gould, G.W., Salt, I.P. J. Biol. Chem. (2003) [Pubmed]
  20. NDPK-A (but not NDPK-B) and AMPK alpha1 (but not AMPK alpha2) bind the cystic fibrosis transmembrane conductance regulator in epithelial cell membranes. Crawford, R.M., Treharne, K.J., Best, O.G., Riemen, C.E., Muimo, R., Gruenert, D.C., Arnaud-Dabernat, S., Daniel, J.Y., Mehta, A. Cell. Signal. (2006) [Pubmed]
  21. AMPK regulation of the growth of cultured human keratinocytes. Saha, A.K., Persons, K., Safer, J.D., Luo, Z., Holick, M.F., Ruderman, N.B. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  22. Semi-quantitative fluorescent PCR analysis identifies PRKAA1 on chromosome 5 as a potential candidate cancer gene of cervical cancer. Huang, F.Y., Chiu, P.M., Tam, K.F., Kwok, Y.K., Lau, E.T., Tang, M.H., Ng, T.Y., Liu, V.W., Cheung, A.N., Ngan, H.Y. Gynecol. Oncol. (2006) [Pubmed]
  23. 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]
  24. LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. Lizcano, J.M., Göransson, O., Toth, R., Deak, M., Morrice, N.A., Boudeau, J., Hawley, S.A., Udd, L., Mäkelä, T.P., Hardie, D.G., Alessi, D.R. EMBO J. (2004) [Pubmed]
  25. Activation of acetyl-CoA carboxylase by a glutamate- and magnesium-sensitive protein phosphatase in the islet beta-cell. Kowluru, A., Chen, H.Q., Modrick, L.M., Stefanelli, C. Diabetes (2001) [Pubmed]
  26. Circulating adiponectin and expression of adiponectin receptors in human skeletal muscle: associations with metabolic parameters and insulin resistance and regulation by physical training. Blüher, M., Bullen, J.W., Lee, J.H., Kralisch, S., Fasshauer, M., Klöting, N., Niebauer, J., Schön, M.R., Williams, C.J., Mantzoros, C.S. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  27. AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation. Chen, Z.P., McConell, G.K., Michell, B.J., Snow, R.J., Canny, B.J., Kemp, B.E. Am. J. Physiol. Endocrinol. Metab. (2000) [Pubmed]
  28. Identification of the sucrose non-fermenting related kinase SNRK, as a novel LKB1 substrate. Jaleel, M., McBride, A., Lizcano, J.M., Deak, M., Toth, R., Morrice, N.A., Alessi, D.R. FEBS Lett. (2005) [Pubmed]
  29. 5-amino-imidazole carboxamide riboside increases glucose transport and cell-surface GLUT4 content in skeletal muscle from subjects with type 2 diabetes. Koistinen, H.A., Galuska, D., Chibalin, A.V., Yang, J., Zierath, J.R., Holman, G.D., Wallberg-Henriksson, H. Diabetes (2003) [Pubmed]
  30. Extracellular adenosine activates AMP-dependent protein kinase (AMPK). Aymerich, I., Foufelle, F., Ferré, P., Casado, F.J., Pastor-Anglada, M. J. Cell. Sci. (2006) [Pubmed]
  31. AMP-activated protein kinase activation by adrenoceptors in L6 skeletal muscle cells: mediation by alpha1-adrenoceptors causing glucose uptake. Hutchinson, D.S., Bengtsson, T. Diabetes (2006) [Pubmed]
  32. Insulin-like Growth Factor-I Signaling Mechanisms, Type I Collagen and Alpha Smooth Muscle Actin in Human Fetal Lung Fibroblasts. Chetty, A., Cao, G.J., Nielsen, H.C. Pediatr. Res. (2006) [Pubmed]
  33. Hypoxia-induced energy stress regulates mRNA translation and cell growth. Liu, L., Cash, T.P., Jones, R.G., Keith, B., Thompson, C.B., Simon, M.C. Mol. Cell (2006) [Pubmed]
  34. Inhibition of germline proliferation during C. elegans dauer development requires PTEN, LKB1 and AMPK signalling. Narbonne, P., Roy, R. Development (2006) [Pubmed]
  35. Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein. Suzuki, A., Kusakai, G., Kishimoto, A., Lu, J., Ogura, T., Lavin, M.F., Esumi, H. J. Biol. Chem. (2003) [Pubmed]
  36. Interaction of the monoclonal antibodies alpha IR-1 and alpha IR-3 with insulin and somatomedin-C receptors. Jacobs, S., Cook, S., Svoboda, M.E., Van Wyk, J.J. Endocrinology (1986) [Pubmed]
  37. 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]
  38. AMPK control of myocardial fatty acid metabolism fluctuates with the intensity of insulin-deficient diabetes. Kewalramani, G., An, D., Kim, M.S., Ghosh, S., Qi, D., Abrahani, A., Pulinilkunnil, T., Sharma, V., Wambolt, R.B., Allard, M.F., Innis, S.M., Rodrigues, B. J. Mol. Cell. Cardiol. (2007) [Pubmed]
  39. 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]
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