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

• Low levels of activation of AMPK are likely to play a role in the current global rise in obesity and Type 2 diabetes, and AMPK is the target for the widely used antidiabetic drug metformin [15].
• Recent data strongly implicate the AMPK-acetyl CoA carboxylase (ACC)-malonyl CoA pathway in the hypothalamus in the regulation of food intake, body weight and hepatic glucose production [16].
• Rather, activation of AMPK alters partitioning of glucose away from glycogen synthesis; the increase in glycolysis may in part contribute to loss of adenosine-induced cardioprotection in hearts subjected to transient ischemia [17].
• These data demonstrate that adenosine-induced activation of AMPK after transient ischemia is not sufficient to alter palmitate oxidation or glucose uptake [17].
• Activation of AMPK during and following ischemia appears to be centrally involved in this decrease in malonyl CoA [18].

Biological context of PRKAA1

• We propose that stimuli that result in the acute activation of AMPK activity in endothelial cells stimulate NO production, at least in part due to phosphorylation and activation of eNOS [19].
• In HEK293 cells, transfection of a dominant-negative AMPK construct abolished the oligomycin-induced inhibition of protein synthesis and eEF2 phosphorylation [1].
• The AMP-activated protein kinase (AMPK) is a heterotrimer composed of different isoforms of the alphabetagamma subunits, where the alpha1 catalytic subunit binds CFTR [20].
• They also suggest that AMPK activators, such as AICAR and troglitazone, inhibit keratinocyte growth and that the inhibition of cell growth by 1,25-dihydroxyvitamin D(3) is AMPK-independent [21].
• Semi-quantitative fluorescent PCR analysis identifies PRKAA1 on chromosome 5 as a potential candidate cancer gene of cervical cancer [22].

Anatomical context of PRKAA1

• The PRKAA1 protein was detected in granulosa cells, COC, DO, and zona pellucida (ZP) [23].
• RT-PCR and immunoblotting revealed the expression of the PRKAA1 subunit in granulosa cells, cumulus-oocyte complexes (COC), and denuded oocytes (DO) [23].
• We therefore determined whether activation of AMPK with 5'-aminoimidazole-4-carboxamide ribonucleoside (AICAR) stimulated NO production in human aortic endothelial cells [19].
• In anoxic rat hepatocytes or in hepatocytes treated with 5-aminoimidazole-4-carboxamide (AICA) riboside, AMPK was activated and protein synthesis was inhibited [1].
• AMP-activated protein kinase (AMPK) has previously been demonstrated to phosphorylate and activate eNOS at Ser-1177 in vitro, yet the function of AMPK in endothelium is poorly characterized [19].

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

• LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1 [24].
• These data suggest that AICAR-stimulated NO production is mediated by AMPK as a consequence of increased Ser-1177 phosphorylation of eNOS [19].
• Activation of AMPK is an attractive strategy to enhance glucose transport through increased cell surface GLUT4 content in insulin-resistant skeletal muscle [29].
• In summary, this study shows that adenosine, when added at physiological concentrations, activates AMPK and promotes ACC phosphorylation [30].
• We further show that glucose uptake mediated by alpha1- but not by beta-adrenoceptors can be inhibited by AMPK inhibition [31].

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

• Using RT-PCR, PRKAA1 mRNA expression in seven tumor samples with known 5p amplification was amplified from 3- to 15-fold [22].
• Finally, feeding mice a low-fat diet with ethanol resulted in significantly reduced hepatic AMPK activity, increased ACC activity, and enhanced malonyl CoA content [2].
• The efficacy of transfection with siRNAs in reducing AMPK content was confirmed by Western blotting [37].
• Given that AMPK plays an important role in preventing cardiac ischemic/reperfusion damage, it is possible that in these diabetic hearts, the accelerated damage observed during exposure to ischemia/reperfusion could be a likely outcome of a compromised activation of AMPK [38].
• Intracerebroventricular CNTF(Ax15) reduced food intake, increased arcuate nucleus (ARC) signal transducer and activator of transcription 3 phosphorylation, and reduced AMPK signaling but not in the paraventricular nucleus (PVN), posterior hypothalamus, or cortex [39].

References