From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
5'-AMP-activated protein kinase catalytic subunit alpha-1 is an
enzyme that in humans is encoded by the PRKAA1
gene .
[5]
[6]
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.
[6] A recent study proposes a role in the metastatic cascade and phenotype determination of pancreatic cancer.
[7]
Interactions
Protein kinase, AMP-activated, alpha 1 has been shown to
interact with
TSC2 .
[8]
[9]
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000132356 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000050697 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Stapleton D, Mitchelhill KI, Gao G, Widmer J, Michell BJ, Teh T, House CM, Fernandez CS, Cox T, Witters LA, Kemp BE (Feb 1996).
"Mammalian AMP-activated protein kinase subfamily" . J Biol Chem . 271 (2): 611–4.
doi :
10.1074/jbc.271.2.611 .
PMID
8557660 .
^
a
b
"Entrez Gene: PRKAA1 protein kinase, AMP-activated, alpha 1 catalytic subunit" .
^ 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 .
doi :
10.1002/advs.202307695 .
ISSN
2198-3844 .
^ Inoki, Ken; Zhu Tianqing; Guan Kun-Liang (Nov 2003).
"TSC2 mediates cellular energy response to control cell growth and survival" . Cell . 115 (5). United States: 577–90.
doi :
10.1016/S0092-8674(03)00929-2 .
ISSN
0092-8674 .
PMID
14651849 .
S2CID
18173817 .
^ 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). United States: 91–9.
doi :
10.1016/j.ccr.2004.06.007 .
ISSN
1535-6108 .
PMID
15261145 .
Further reading
Munday MR, Campbell DG, Carling D, Hardie DG (1988).
"Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase" . Eur. J. Biochem . 175 (2): 331–8.
doi :
10.1111/j.1432-1033.1988.tb14201.x .
PMID
2900138 .
Woods A, Cheung PC, Smith FC, et al. (1996).
"Characterization of AMP-activated protein kinase beta and gamma subunits. Assembly of the heterotrimeric complex in vitro" . J. Biol. Chem . 271 (17): 10282–90.
doi :
10.1074/jbc.271.48.30517 .
PMID
8626596 .
Hawley SA, Davison M, Woods A, et al. (1996).
"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.
doi :
10.1074/jbc.271.44.27879 .
PMID
8910387 .
Stapleton D, Woollatt E, Mitchelhill KI, et al. (1997). "AMP-activated protein kinase isoenzyme family: subunit structure and chromosomal location". FEBS Lett . 409 (3): 452–6.
doi :
10.1016/S0014-5793(97)00569-3 .
PMID
9224708 .
S2CID
39329574 .
Velasco G, Gómez del Pulgar T, Carling D, Guzmán M (1998).
"Evidence that the AMP-activated protein kinase stimulates rat liver carnitine palmitoyltransferase I by phosphorylating cytoskeletal components" . FEBS Lett . 439 (3): 317–20.
doi :
10.1016/S0014-5793(98)01400-8 .
PMID
9845345 .
S2CID
29493620 .
Crute BE, Seefeld K, Gamble J, et al. (1999).
"Functional domains of the alpha1 catalytic subunit of the AMP-activated protein kinase" . J. Biol. Chem . 273 (52): 35347–54.
doi :
10.1074/jbc.273.52.35347 .
PMID
9857077 .
da Silva Xavier G, Leclerc I, Salt IP, et al. (2000).
"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.
Bibcode :
2000PNAS...97.4023D .
doi :
10.1073/pnas.97.8.4023 .
PMC
18135 .
PMID
10760274 .
Hallows KR, Raghuram V, Kemp BE, et al. (2000).
"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.
doi :
10.1172/JCI9622 .
PMC
378514 .
PMID
10862786 .
Zhang QH, Ye M, Wu XY, et al. (2001).
"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.
doi :
10.1101/gr.140200 .
PMC
310934 .
PMID
11042152 .
Chen ZP, McConell GK, Michell BJ, et al. (2000). "AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation". Am. J. Physiol. Endocrinol. Metab . 279 (5): E1202–6.
doi :
10.1152/ajpendo.2000.279.5.E1202 .
PMID
11052978 .
S2CID
13387968 .
Blázquez C, Geelen MJ, Velasco G, Guzmán M (2001).
"The AMP-activated protein kinase prevents ceramide synthesis de novo and apoptosis in astrocytes" . FEBS Lett . 489 (2–3): 149–53.
doi :
10.1016/S0014-5793(01)02089-0 .
PMID
11165240 .
S2CID
35584617 .
Diggle TA, Subkhankulova T, Lilley KS, et al. (2001).
"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.
doi :
10.1042/0264-6021:3530621 .
PMC
1221608 .
PMID
11171059 .
Wang X, Li W, Williams M, et al. (2001).
"Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase" . EMBO J . 20 (16): 4370–9.
doi :
10.1093/emboj/20.16.4370 .
PMC
125559 .
PMID
11500364 .
Xi X, Han J, Zhang JZ (2001).
"Stimulation of glucose transport by AMP-activated protein kinase via activation of p38 mitogen-activated protein kinase" . J. Biol. Chem . 276 (44): 41029–34.
doi :
10.1074/jbc.M102824200 .
PMID
11546797 .
Fryer LG, Foufelle F, Barnes K, et al. (2002).
"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.
doi :
10.1042/0264-6021:3630167 .
PMC
1222463 .
PMID
11903059 .
Yang CS, Weiner H (2002). "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.
doi :
10.1006/abbi.2002.2778 .
PMID
11913976 .
Bolster DR, Crozier SJ, Kimball SR, Jefferson LS (2002).
"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.
doi :
10.1074/jbc.C200171200 .
PMID
11997383 .
Esumi H, Izuishi K, Kato K, et al. (2002).
"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.
doi :
10.1074/jbc.M112270200 .
PMID
12091379 .
Horman S, Browne G, Krause U, et al. (2003).
"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.
doi :
10.1016/S0960-9822(02)01077-1 .
PMID
12194824 .
S2CID
9865400 .
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)
Activity Regulation Classification Kinetics Types