D
IPR039137

5'-AMP-activated protein kinase alpha 1 catalytic subunit, C-terminal

InterPro entry
Short nameAMPKA1_C
Overlapping
homologous
superfamilies
 

Description

AMPK, a serine/threonine protein kinase (STK), catalyzes the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. It acts as a sensor for the energy status of the cell and is activated by cellular stresses that lead to ATP depletion such as hypoxia, heat shock, and glucose deprivation, among others. AMPK is a heterotrimer of three subunits: alpha, beta, and gamma
[1]
. The alpha subunit is the catalytic subunit and it contains an N-terminal kinase domain, a putative autoinhibitory domain (AID) and a C-terminal region required for beta subunit binding. The beta scaffolding subunit mediates AMPK assembly by bridging alpha and gamma subunits. The C-terminal domain of the AMPK alpha 1 subunit interacts with the C-terminal region of the beta subunit to form a tight alpha-beta complex that is associated with the gamma subunit. The AMPK alpha subunit auto-inhibitory region interacts with the kinase domain; this inhibition is negated by the interaction with the AMPK gamma subunit
[2]
.

AMPK has been implicated in a number of diseases related to energy metabolism including type 2 diabetes, obesity and cancer
[8, 7]
. AMPK is activated by rising AMP concentrations coupled with falling ATP concentrations. Activation of AMPK is also dependent on the phosphorylation of alpha subunit by upstream kinases such as LKB1
[3]
.

Vertebrates contain two isoforms of the alpha subunit, alpha1 and alpha2, which are encoded by different genes, PRKAA1 and PRKAA2, respectively, and show varying expression patterns. AMPKalpha1 is the predominant isoform expressed in bone; it plays a role in bone remodeling in response to hormonal regulation
[4]
. AMPK alpha1 impacts the regulation of fat metabolism
[6]
. It also mediates the vasoprotective effects of estrogen through phosphorylation of another in vivo substrate, RhoA
[5]
.

References

1.AMP-activated protein kinase: structure and regulation. Sanz P. Curr. Protein Pept. Sci. 9, 478-92, (2008). View articlePMID: 18855699

2.Structural insights into the architecture and allostery of full-length AMP-activated protein kinase. Zhu L, Chen L, Zhou XM, Zhang YY, Zhang YJ, Zhao J, Ji SR, Wu JW, Wu Y. Structure 19, 515-22, (2011). View articlePMID: 21481774

3.LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LG, Neumann D, Schlattner U, Wallimann T, Carlson M, Carling D. Curr. Biol. 13, 2004-8, (2003). View articlePMID: 14614828

4.Mice lacking AMP-activated protein kinase α1 catalytic subunit have increased bone remodelling and modified skeletal responses to hormonal challenges induced by ovariectomy and intermittent PTH treatment. Jeyabalan J, Shah M, Viollet B, Roux JP, Chavassieux P, Korbonits M, Chenu C. J. Endocrinol. 214, 349-58, (2012). View articlePMID: 22700192

5.AMPK alpha 1-induced RhoA phosphorylation mediates vasoprotective effect of estradiol. Gayard M, Guilluy C, Rousselle A, Viollet B, Henrion D, Pacaud P, Loirand G, Rolli-Derkinderen M. Arterioscler. Thromb. Vasc. Biol. 31, 2634-42, (2011). View articlePMID: 21852563

6.Muscle-specific deletion of Prkaa1 enhances skeletal muscle lipid accumulation in mice fed a high-fat diet. Wu W, Xu Z, Zhang L, Liu J, Feng J, Wang X, Shan T, Wang Y. J. Physiol. Biochem. (2017). View articlePMID: 29288408

7.The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Shackelford DB, Shaw RJ. Nat. Rev. Cancer 9, 563-75, (2009). View articlePMID: 19629071

8.Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cool B, Zinker B, Chiou W, Kifle L, Cao N, Perham M, Dickinson R, Adler A, Gagne G, Iyengar R, Zhao G, Marsh K, Kym P, Jung P, Camp HS, Frevert E. Cell Metab. 3, 403-16, (2006). View articlePMID: 16753576

GO terms

biological process

  • None

cellular component

  • None

Cross References

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