Protein kinase, AMP-activated, alpha 1 explained

5'-AMP-activated protein kinase catalytic subunit alpha-1 is an enzyme that in humans is encoded by the PRKAA1 gene.^{[1] [2]}

The protein encoded by this gene belongs to the serine/threonine protein kinase family. It is the catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor conserved in all eukaryotic cells. The kinase activity of AMPK is activated by the stimuli that increase the cellular AMP/ATP ratio. AMPK regulates the activities of a number of key metabolic enzymes through phosphorylation. It protects cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. Alternatively spliced transcript variants encoding distinct isoforms have been observed.^[2] A recent study proposes a role in the metastatic cascade and phenotype determination of pancreatic cancer.^[3]

Interactions

Protein kinase, AMP-activated, alpha 1 has been shown to interact with TSC2.^{[4] [5]}

Further reading

• Munday MR, Campbell DG, Carling D, Hardie DG . Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase. . Eur. J. Biochem. . 175 . 2 . 331–8 . 1988 . 2900138 . 10.1111/j.1432-1033.1988.tb14201.x . free .
• Woods A, Cheung PC, Smith FC, etal . Characterization of AMP-activated protein kinase beta and gamma subunits. Assembly of the heterotrimeric complex in vitro. . J. Biol. Chem. . 271 . 17 . 10282–90 . 1996 . 8626596 . 10.1074/jbc.271.48.30517. free .
• Hawley SA, Davison M, Woods A, etal . Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase. . J. Biol. Chem. . 271 . 44 . 27879–87 . 1996 . 8910387 . 10.1074/jbc.271.44.27879 . free .
• Stapleton D, Woollatt E, Mitchelhill KI, etal . AMP-activated protein kinase isoenzyme family: subunit structure and chromosomal location. . FEBS Lett. . 409 . 3 . 452–6 . 1997 . 9224708 . 10.1016/S0014-5793(97)00569-3. 39329574 .
• Velasco G, Gómez del Pulgar T, Carling D, Guzmán M . Evidence that the AMP-activated protein kinase stimulates rat liver carnitine palmitoyltransferase I by phosphorylating cytoskeletal components. . FEBS Lett. . 439 . 3 . 317–20 . 1998 . 9845345 . 10.1016/S0014-5793(98)01400-8 . 29493620 . free .
• Crute BE, Seefeld K, Gamble J, etal . Functional domains of the alpha1 catalytic subunit of the AMP-activated protein kinase. . J. Biol. Chem. . 273 . 52 . 35347–54 . 1999 . 9857077 . 10.1074/jbc.273.52.35347 . free .
• da Silva Xavier G, Leclerc I, Salt IP, etal . Role of AMP-activated protein kinase in the regulation by glucose of islet beta cell gene expression. . Proc. Natl. Acad. Sci. U.S.A. . 97 . 8 . 4023–8 . 2000 . 10760274 . 18135 . 10.1073/pnas.97.8.4023. 2000PNAS...97.4023D . free .
• Hallows KR, Raghuram V, Kemp BE, etal . Inhibition of cystic fibrosis transmembrane conductance regulator by novel interaction with the metabolic sensor AMP-activated protein kinase. . J. Clin. Invest. . 105 . 12 . 1711–21 . 2000 . 10862786 . 378514 . 10.1172/JCI9622.
• Zhang QH, Ye M, Wu XY, etal . Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. . Genome Res. . 10 . 10 . 1546–60 . 2001 . 11042152 . 310934 . 10.1101/gr.140200.
• Chen ZP, McConell GK, Michell BJ, etal . AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation. . Am. J. Physiol. Endocrinol. Metab. . 279 . 5 . E1202–6 . 2000 . 11052978 . 10.1152/ajpendo.2000.279.5.E1202. 13387968 .
• Blázquez C, Geelen MJ, Velasco G, Guzmán M . The AMP-activated protein kinase prevents ceramide synthesis de novo and apoptosis in astrocytes. . FEBS Lett. . 489 . 2–3 . 149–53 . 2001 . 11165240 . 10.1016/S0014-5793(01)02089-0 . 35584617 . free .
• Diggle TA, Subkhankulova T, Lilley KS, etal . Phosphorylation of elongation factor-2 kinase on serine 499 by cAMP-dependent protein kinase induces Ca2+/calmodulin-independent activity. . Biochem. J. . 353 . Pt 3 . 621–6 . 2001 . 11171059 . 1221608 . 10.1042/0264-6021:3530621 .
• Wang X, Li W, Williams M, etal . Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase. . EMBO J. . 20 . 16 . 4370–9 . 2001 . 11500364 . 125559 . 10.1093/emboj/20.16.4370 .
• Xi X, Han J, Zhang JZ . Stimulation of glucose transport by AMP-activated protein kinase via activation of p38 mitogen-activated protein kinase. . J. Biol. Chem. . 276 . 44 . 41029–34 . 2001 . 11546797 . 10.1074/jbc.M102824200 . free .
• Fryer LG, Foufelle F, Barnes K, etal . Characterization of the role of the AMP-activated protein kinase in the stimulation of glucose transport in skeletal muscle cells. . Biochem. J. . 363 . Pt 1 . 167–74 . 2002 . 11903059 . 1222463 . 10.1042/0264-6021:3630167 .
• Yang CS, Weiner H . Yeast two-hybrid screening identifies binding partners of human Tom34 that have ATPase activity and form a complex with Tom34 in the cytosol. . Arch. Biochem. Biophys. . 400 . 1 . 105–10 . 2002 . 11913976 . 10.1006/abbi.2002.2778 .
• Bolster DR, Crozier SJ, Kimball SR, Jefferson LS . AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. . J. Biol. Chem. . 277 . 27 . 23977–80 . 2002 . 11997383 . 10.1074/jbc.C200171200 . free .
• Esumi H, Izuishi K, Kato K, etal . Hypoxia and nitric oxide treatment confer tolerance to glucose starvation in a 5'-AMP-activated protein kinase-dependent manner. . J. Biol. Chem. . 277 . 36 . 32791–8 . 2002 . 12091379 . 10.1074/jbc.M112270200 . free .
• Horman S, Browne G, Krause U, etal . Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. . Curr. Biol. . 12 . 16 . 1419–23 . 2003 . 12194824 . 10.1016/S0960-9822(02)01077-1 . 9865400 . free .

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)

Notes and References

1. Stapleton D, Mitchelhill KI, Gao G, Widmer J, Michell BJ, Teh T, House CM, Fernandez CS, Cox T, Witters LA, Kemp BE . Mammalian AMP-activated protein kinase subfamily . J Biol Chem . 271 . 2 . 611–4 . Feb 1996 . 8557660 . 10.1074/jbc.271.2.611. free .
2. Web site: Entrez Gene: PRKAA1 protein kinase, AMP-activated, alpha 1 catalytic subunit.
3. Schneider . Carolin . Hilbert . Jorina . Genevaux . Franziska . Höfer . Stefanie . Krauß . Lukas . Schicktanz . Felix . Contreras . Constanza Tapia . Jansari . Shaishavi . Papargyriou . Aristeidis . Richter . Thorsten . Alfayomy . Abdallah M. . Falcomatà . Chiara . Schneeweis . Christian . Orben . Felix . Öllinger . Ruppert . 2024-06-17 . A Novel AMPK Inhibitor Sensitizes Pancreatic Cancer Cells to Ferroptosis Induction . Advanced Science . en . 10.1002/advs.202307695 . 2198-3844. free .
4. Inoki . Ken . Zhu Tianqing . Guan Kun-Liang . Nov 2003 . TSC2 mediates cellular energy response to control cell growth and survival . Cell . 115 . 5 . 577–90 . United States. 0092-8674. 14651849 . 10.1016/S0092-8674(03)00929-2. 18173817 . free .
5. Shaw . Reuben J . Bardeesy Nabeel . Manning Brendan D . Lopez Lyle . Kosmatka Monica . DePinho Ronald A . Cantley Lewis C . Jul 2004 . The LKB1 tumor suppressor negatively regulates mTOR signaling . Cancer Cell . 6 . 1 . 91–9 . United States. 1535-6108. 15261145 . 10.1016/j.ccr.2004.06.007 . free .