FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2010284467> ?p ?o ?g. }

• W2010284467 endingPage "7252" @default.
• W2010284467 startingPage "7244" @default.
• W2010284467 abstract "AMP-activated protein kinase (AMPK) is an evolutionarily conserved heterotrimer important for metabolic sensing in all eukaryotes. The muscle-specific isoform of the regulatory γ-subunit of the kinase, AMPK γ3, has an important role in glucose uptake, glycogen synthesis, and fat oxidation in white skeletal muscle, as previously demonstrated by physiological characterization of AMPK γ3 mutant (R225Q) transgenic (TgPrkag3225Q) and γ3 knock-out (Prkag3-/-) mice. We determined AMPK γ3-dependent regulation of gene expression by analyzing global transcription profiles in glycolytic skeletal muscle from γ3 mutant transgenic and knock-out mice using oligonucleotide microarray technology. Evidence is provided for coordinated and reciprocal regulation of multiple key components in glucose and fat metabolism, as well as skeletal muscle ergogenics in TgPrkag3225Q and Prkag3-/- mice. The differential gene expression profile was consistent with the physiological differences between the models, providing a molecular mechanism for the observed phenotype. The striking pattern of opposing transcriptional changes between TgPrkag3225Q and Prkag3-/- mice identifies differentially expressed targets being truly regulated by AMPK and is consistent with the view that R225Q is an activating mutation, in terms of its downstream effects. Additionally, we identified a wide array of novel targets and regulatory pathways for AMPK in skeletal muscle. AMP-activated protein kinase (AMPK) is an evolutionarily conserved heterotrimer important for metabolic sensing in all eukaryotes. The muscle-specific isoform of the regulatory γ-subunit of the kinase, AMPK γ3, has an important role in glucose uptake, glycogen synthesis, and fat oxidation in white skeletal muscle, as previously demonstrated by physiological characterization of AMPK γ3 mutant (R225Q) transgenic (TgPrkag3225Q) and γ3 knock-out (Prkag3-/-) mice. We determined AMPK γ3-dependent regulation of gene expression by analyzing global transcription profiles in glycolytic skeletal muscle from γ3 mutant transgenic and knock-out mice using oligonucleotide microarray technology. Evidence is provided for coordinated and reciprocal regulation of multiple key components in glucose and fat metabolism, as well as skeletal muscle ergogenics in TgPrkag3225Q and Prkag3-/- mice. The differential gene expression profile was consistent with the physiological differences between the models, providing a molecular mechanism for the observed phenotype. The striking pattern of opposing transcriptional changes between TgPrkag3225Q and Prkag3-/- mice identifies differentially expressed targets being truly regulated by AMPK and is consistent with the view that R225Q is an activating mutation, in terms of its downstream effects. Additionally, we identified a wide array of novel targets and regulatory pathways for AMPK in skeletal muscle. AMP-activated protein kinase (AMPK) 2The abbreviations used are: AMPK, AMP-activated protein kinase; RN, Rendement Napole; qRT-PCR, quantitative real-time PCR; EST, expressed sequence tag; MAPK, mitogen-activate protein kinase; AICAR, 5-amino-4-imidazole-carboxamide riboside.2The abbreviations used are: AMPK, AMP-activated protein kinase; RN, Rendement Napole; qRT-PCR, quantitative real-time PCR; EST, expressed sequence tag; MAPK, mitogen-activate protein kinase; AICAR, 5-amino-4-imidazole-carboxamide riboside. is a critical regulator of carbohydrate and fat metabolism in eukaryotic cells (reviewed in Refs. 1Carling D. Trends Biochem. Sci. 2004; 29: 18-24Abstract Full Text Full Text PDF PubMed Scopus (947) Google Scholar and 2Hardie D.G. J. Cell. Sci. 2004; 117: 5479-5487Crossref PubMed Scopus (954) Google Scholar). AMPK is a heterotrimer that consists of α-, β-, and γ-subunits, all of which are required for its activity. The catalytic α-subunit contains a conventional serine/threonine protein kinase domain, and phosphorylation of Thr-172 residue within the activation loop of the α-subunit by upstream kinases is essential for the activity of the heterotrimer (3Hawley S.A. Boudeau J. Reid J.L. Mustard K.J. Udd L. Makela T.P. Alessi D.R. Hardie D.G. J. Biol. 2003; 2: 28Crossref PubMed Google Scholar, 4Hong S.P. Leiper F.C. Woods A. Carling D. Carlson M. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 8839-8843Crossref PubMed Scopus (469) Google Scholar, 5Hawley S.A. Pan D.A. Mustard K.J. Ross L. Bain J. Edelman A.M. Frenguelli B.G. Hardie D.G. Cell. Metab. 2005; 2: 9-19Abstract Full Text Full Text PDF PubMed Scopus (1259) Google Scholar, 6Woods A. Dickerson K. Heath R. Hong S.P. Momcilovic M. Johnstone S.R. Carlson M. Carling D. Cell. Metab. 2005; 2: 21-33Abstract Full Text Full Text PDF PubMed Scopus (1052) Google Scholar). Once phosphorylated at Thr-172, AMPK can be further activated by allosteric binding of AMP to the evolutionary conserved cystathionine β-synthase domains in the regulatory γ-subunit (7Scott J.W. Hawley S.A. Green K.A. Anis M. Stewart G. Scullion G.A. Norman D.G. Hardie D.G. J. Clin. Invest. 2004; 113: 274-284Crossref PubMed Scopus (599) Google Scholar). The AMPK β-subunit acts as a scaffold for binding of the α- and γ-subunits (8Woods A. Cheung P.C. Smith F.C. Davison M.D. Scott J. Beri R.K. Carling D. J. Biol. Chem. 1996; 271: 10282-10290Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar). The β-subunit also contains a glycogen-binding domain, and recent findings provide evidence that this motif is involved in targeting the AMPK complex to cellular glycogen stores (9Hudson E.R. Pan D.A. James J. Lucocq J.M. Hawley S.A. Green K.A. Baba O. Terashima T. Hardie D.G. Curr. Biol. 2003; 13: 861-866Abstract Full Text Full Text PDF PubMed Scopus (274) Google Scholar, 10Polekhina G. Gupta A. Michell B.J. van Denderen B. Murthy S. Feil S.C. Jennings I.G. Campbell D.J. Witters L.A. Parker M.W. Kemp B.E. Stapleton D. Curr. Biol. 2003; 13: 867-871Abstract Full Text Full Text PDF PubMed Scopus (351) Google Scholar). The mammalian genome contains seven AMPK genes encoding for two α-, two β-, and three γ-isoforms. Thus, there are 12 possible combinations of heterotrimeric AMPK, and the physiological function of the AMPK holoenzyme depends on the particular isoforms present in the complex.We have provided evidence that AMPK γ3 is the predominant γ-isoform expressed in glycolytic (white, fast-twitch type II) skeletal muscle (11Mahlapuu M. Johansson C. Lindgren K. Hjalm G. Barnes B.R. Krook A. Zierath J.R. Andersson L. Marklund S. Am. J. Physiol. 2004; 286: E194-E200Crossref PubMed Scopus (147) Google Scholar). In contrast, it is expressed at low levels in oxidative (red, slow-twitch type I) skeletal muscle and is undetectable in brain, liver, heart, or white adipose tissue (11Mahlapuu M. Johansson C. Lindgren K. Hjalm G. Barnes B.R. Krook A. Zierath J.R. Andersson L. Marklund S. Am. J. Physiol. 2004; 286: E194-E200Crossref PubMed Scopus (147) Google Scholar). Thus, the AMPK γ3-subunit is the only isoform exhibiting tissue-specific expression. Furthermore, the AMPK γ3-subunit primarily forms heterotrimers with the α2- and β2-isoforms in glycolytic skeletal muscle (11Mahlapuu M. Johansson C. Lindgren K. Hjalm G. Barnes B.R. Krook A. Zierath J.R. Andersson L. Marklund S. Am. J. Physiol. 2004; 286: E194-E200Crossref PubMed Scopus (147) Google Scholar).The functional significance of the AMPK γ3-subunit has been demonstrated by phenotypic analysis of animal models carrying a mutated form of the gene. The dominant Rendement Napole (RN) phenotype identified in Hampshire pigs is caused by a single missense mutation (R225Q) in the AMPK γ3-subunit (12Milan D. Jeon J.T. Looft C. Amarger V. Robic A. Thelander M. Rogel-Gaillard C. Paul S. Iannuccelli N. Rask L. Ronne H. Lundstrom K. Reinsch N. Gellin J. Kalm E. Roy P.L. Chardon P. Andersson L. Science. 2000; 288: 1248-1251Crossref PubMed Scopus (605) Google Scholar). RN pigs have a 70% increase in glycogen content in skeletal muscle, whereas liver and heart glycogen content remains unchanged (13Estrade M. Vignon X. Rock E. Monin G. Comp. Biochem. Physiol. B. 1993; 104: 321-326Crossref PubMed Scopus (53) Google Scholar). Furthermore, RN carriers are also characterized by a higher oxidative capacity in white skeletal muscle fibers (14Estrade M. Ayoub S. Talmant A. Monin G. Comp. Biochem. Physiol. Biochem. Mol. Biol. 1994; 108: 295-301Crossref PubMed Scopus (38) Google Scholar, 15Lebret B. Le Roy P. Monin G. Lefaucheur L. Caritez J.C. Talmant A. Elsen J.M. Sellier P. J. Anim. Sci. 1999; 77: 1482-1489Crossref PubMed Scopus (89) Google Scholar). Conversely, a second mutation (V224I) identified in pigs at the neighboring amino acid residue of the γ3-protein is associated with an opposite phenotype compared with the RN allele, resulting in reduced skeletal muscle glycogen content (16Ciobanu D. Bastiaansen J. Malek M. Helm J. Woollard J. Plastow G. Rothschild M. Genetics. 2001; 159: 1151-1162Crossref PubMed Google Scholar). Characterization of transgenic mice with skeletal muscle-specific expression of the mutant (R225Q) form of the mouse AMPK γ3-subunit, as well as AMPK γ3-subunit knock-out mice, provided further evidence that the γ3-subunit plays a key role in skeletal muscle carbohydrate and lipid metabolism. Glycogen resynthesis after exercise was impaired in AMPK γ3 knock-out mice but was markedly enhanced in transgenic mutant mice. An AMPK-activator failed to increase skeletal muscle glucose uptake in knock-out mice, whereas insulin-mediated glucose uptake was unaltered. When fed with a high fat diet, γ3 R225Q transgenic mice were protected against excessive triglyceride accumulation and insulin resistance in skeletal muscle, presumably due to an increase in fat oxidation (17Barnes B.R. Marklund S. Steiler T.L. Walter M. Hjalm G. Amarger V. Mahlapuu M. Leng Y. Johansson C. Galuska D. Lindgren K. Abrink M. Stapleton D. Zierath J.R. Andersson L. J. Biol. Chem. 2004; 279: 38441-38447Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar). Additionally, skeletal muscle from γ3 R225Q mutant mice is characterized by enhanced work performance, whereas knock-out mice are fatigue-prone (18Barnes B.R. Glund S. Long Y.C. Hjalm G. Andersson L. Zierath J.R. FASEB J. 2005; 19: 773-779Crossref PubMed Scopus (64) Google Scholar).To further characterize the role of AMPK γ3 in skeletal muscle and to uncover molecular mechanisms explaining phenotypic consequences of the mutations in this isoform, we have studied AMPK γ3-dependent gene transcription by a systematic approach, using global analysis of the mRNA expression pattern in the skeletal muscle of γ3 R225Q mutant and γ3 knock-out mice. Here we describe distinct biomarker patterns, comprising AMPK γ3-dependent transcriptional changes of genes involved in glucose and lipid metabolism and skeletal muscle ergogenics.EXPERIMENTAL PROCEDURESAMPK Knock-out (Prkag3-/-) and R225Q Transgenic (TgPrkag3225Q) Mice—The Prkag3-/- and TgPrkag3225Q mice used in this study have been previously described (17Barnes B.R. Marklund S. Steiler T.L. Walter M. Hjalm G. Amarger V. Mahlapuu M. Leng Y. Johansson C. Galuska D. Lindgren K. Abrink M. Stapleton D. Zierath J.R. Andersson L. J. Biol. Chem. 2004; 279: 38441-38447Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar). Prkag3-/- mice were created by conventional gene targeting techniques. TgPrkag3225Q mice express the mutant γ3 R225Q subunit under the control of mouse myosin-light chain promoter and enhancer elements. Mice used in the study were bred into the C57BL/6 genetic background. Mice were maintained in a 12-h light-dark cycle and were cared for in accordance with regulations for the protection of laboratory animals. The study was performed after prior approval from the local ethical committee. Gene expression profiles were characterized in male mice fasted overnight (food was removed 16 h prior to study). The white portion of the gastrocnemius muscle was dissected from anesthetized mice, cleaned of fat and blood, and quickly frozen in liquid nitrogen as described (17Barnes B.R. Marklund S. Steiler T.L. Walter M. Hjalm G. Amarger V. Mahlapuu M. Leng Y. Johansson C. Galuska D. Lindgren K. Abrink M. Stapleton D. Zierath J.R. Andersson L. J. Biol. Chem. 2004; 279: 38441-38447Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar).Preparation of Total RNA—Total RNA was isolated from the white portion of the gastrocnemius muscle using the RNeasy Fibrous Mini Kit (Qiagen) applying Mixer Mill MM 301 (Retsch) followed by a DNase digestion step using RNase-Free DNase Set (Qiagen) according to the manufacturer's instructions. The RNA yield was quantified by spectrophotometric analysis and the RNA purity was determined based on the A260/A280 ratio. The quality of the RNA was confirmed by Agilent 2100 Bioanalyzer analysis (Agilent Technologies) using the RNA 6000 Nano Assay Kit (Agilent Technologies).Preparation of cRNA, Gene Chip Hybridization—10 μg of total RNA spiked with poly-A controls (pGIBS-TRP, -THR, and -LYS, American Type Culture Collection) was converted to cDNA utilizing a T7 promoter-polyT primer (Affymetrix) and the reverse transcriptase Superscript II (Invitrogen), followed by a second strand cDNA synthesis (Invitrogen). Double-stranded cDNA was in vitro transcribed to biotinylated cRNA (Enzo) and then fragmented (Invitrogen). The fragmented cRNA was mixed with control oligonucleotide B2 (Affymetrix) and a hybridization control cRNA mixture (BioB, BioC, BioD, and Cre, Affymetrix). Aliquots of each sample were hybridized (16 h at 45 °C) to GeneChip Mouse Expression Set 430A arrays (Affymetrix). The arrays were subsequently washed, stained, and scanned according the manufacturer's instructions (GeneChip Expression Analysis Technical Manual, Affymetrix).Data Analysis—Data were analyzed using GeneTraffic UNO 3.2-11 (Iobion Informatics) and Spotfire DecisionSite 8.1 (Spotfire Inc.). The TgPrkag3225Q dataset was analyzed separately from the Prkag3-/- dataset. For further details see the supplemental information.Quantitative Real-time PCR—Quantification of mRNA levels for selected genes was performed by qRT-PCR as described (19Applied Biosystems User Bulletin #2 ABI PRISM 7700 Sequence Detection System. Applied Biosystems, Warrington, UK1997Google Scholar) using acidic ribosomal phosphoprotein P0 (Arbp) as endogenous control (see supplemental Table SI for primer information). qRT-PCR was performed on extended set of samples including 7 Prkag3-/- mice with 8 wild-type littermates and 13 TgPrkag3225Q mice with 10 wild-type littermates, while RNA from 6 animals in each group was used in gene array analysis.Histochemistry—Enzyme activity staining for succinate dehydrogenase and cytochrome c oxidase was done on serial cross-sections (10-μm thickness) of frozen gastrocnemius muscle as described previously (20Blanco C.E. Sieck G.C. Edgerton V.R. Histochem. J. 1988; 20: 230-243Crossref PubMed Scopus (117) Google Scholar, 21Seligman A.M. Karnovsky M.J. Wasserkrug H.L. Hanker J.S. J. Cell. Biol. 1968; 38: 1-14Crossref PubMed Scopus (723) Google Scholar). For succinate dehydrogenase activity staining, sections were incubated for 4 min in a 0.1 m phosphate buffer (pH 7.6) containing 5 mm EDTA, 45 mm disodium succinate, 1.2 mm nitro blue tetrazolium, 1 mm potassium cyanide, and 1 mm phenazine methosulfate. Cytochrome c oxidase activity staining was performed by incubating sections for 1 h in a 50 mm phosphate buffer (pH 7.6) containing 0.22 m sucrose, 2.3 mm 3,3′-diaminobenzidine tetrahydrochloride, 1 mm cytochrome c, and 1300 units of catalase.RESULTSMicroarray Analysis of the mRNA Expression in the Skeletal Muscle of AMPK γ3 Knock-out (Prkag3-/-) and R225Q Transgenic (TgPrkag3225Q) Mice—To determine the role of γ3-containing AMPK complexes in regulation of gene expression in the skeletal muscle, we utilized mouse models that either lack the AMPK γ3-protein (Prkag3-/-) or express a R225Q mutant form of this protein in skeletal muscle (TgPrkag3225Q) (17Barnes B.R. Marklund S. Steiler T.L. Walter M. Hjalm G. Amarger V. Mahlapuu M. Leng Y. Johansson C. Galuska D. Lindgren K. Abrink M. Stapleton D. Zierath J.R. Andersson L. J. Biol. Chem. 2004; 279: 38441-38447Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar). In Prkag3-/- mice, AMPK γ3-protein expression is completely ablated, and importantly, no compensatory increase in γ1- or γ2-isoform is detected (17Barnes B.R. Marklund S. Steiler T.L. Walter M. Hjalm G. Amarger V. Mahlapuu M. Leng Y. Johansson C. Galuska D. Lindgren K. Abrink M. Stapleton D. Zierath J.R. Andersson L. J. Biol. Chem. 2004; 279: 38441-38447Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar). Equally important, AMPK expression in TgPrkag3225Q mice resembles the expression pattern in wild-type mice, both with regard to tissue distribution and protein expression, with the mutant (R225Q) form replacing the endogenous AMPK γ3-protein (17Barnes B.R. Marklund S. Steiler T.L. Walter M. Hjalm G. Amarger V. Mahlapuu M. Leng Y. Johansson C. Galuska D. Lindgren K. Abrink M. Stapleton D. Zierath J.R. Andersson L. J. Biol. Chem. 2004; 279: 38441-38447Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar). Global gene expression profiles in the white portion of gastrocnemius muscle of Prkag3-/- and TgPrkag3225Q mice were compared with the corresponding wild-type littermates using oligonucleotide microarrays. The expression of 167 genes was significantly (p ≤ 0.05) changed by a factor of 20% or more, in TgPrkag3225Q and/or Prkag3-/- mice, relative to the wild-type controls (Table 1). Applying the same filtering criteria on randomly created groups within the Prkag3-/- dataset and TgPrkag3225Q dataset resulted in six genes determined as differentially expressed. This indicates that the rate of false positives is low. Consequently, the vast majority of the genes appearing differently expressed in Prkag3-/- and/or TgPrkag3225Q mice can be considered as truly regulated.TABLE 1Differentially expressed genes in TgPrkag3225Q and/or Prkag3-/- mice compared with wild-type littermates Global mRNA expression pattern was characterized in the white portion of the gastrocnemius skeletal muscle in male mice of C57BL/6 genetic background. The filtering criteria were set to a mean absolute -fold change >1.2 and a p value ≤0.05. In addition the mean intensity in the group showing highest expression should be >75.Public IDGene symbolGene titleTgPrkag3225Q versus wild-type littermatesPrkag3-/- versus wild-type littermates-Fold changep value-Fold changep valueGenes differentially expressed in both TgPrkag3225Q and Prkag3-/- compared with wild-type littermatesAU017649Gdap1aGenes having several probe sets supporting the regulationGanglioside-induced differentiation-associated-protein 1-1.820.00041.270.003BB336256Mafav-maf musculoaponeurotic fibrosarcoma oncogene family, protein A-1.580.0000081.290.002BC026377Rasd2aGenes having several probe sets supporting the regulationRASD family, member 21.530.00005-1.210.048NM_010016Daf1aGenes having several probe sets supporting the regulationDecay accelerating factor 11.500.002-1.200.018M62838Slc7a2aGenes having several probe sets supporting the regulationSolute carrier family 7, member 21.460.006-1.350.023BB414515Slc2a3aGenes having several probe sets supporting the regulationSolute carrier family 2, member 3-1.420.0021.220.035BB326929Sh3kbp1SH3-domain kinase binding protein 11.410.010-1.230.011NM_028803Gbe1Glucan branching enzyme 11.400.012-1.280.011AI788759Ugp2aGenes having several probe sets supporting the regulationUDP-glucose pyrophosphorylase 21.390.0001-1.210.008AF226613Slc40a1Solute carrier family 40, member 11.380.006-1.260.019NM_009876Cdkn1cCyclin-dependent kinase inhibitor 1C-1.320.00051.200.022AV337591Xpr1Xenotropic and polytropic retrovirus receptor 1-1.260.0091.210.005BM114165Rpl5Ribosomal protein L5-1.240.0151.210.024NM_009079Rpl22Ribosomal protein L22-1.240.0071.200.00004AV0306032010109N14RikRIKEN clone 2010109N14-1.220.0101.210.037BC011152Golph2Golgi phosphoprotein 2-1.220.0031.250.002Genes differentially expressed in TgPrkag3225Q compared with wild-type littermatesNM_007913Egr1Mus musculus early growth response 12.360.021-1.050.887BC024613Tmem37M. musculus transmembrane protein 372.030.0000071.160.375NM_008161Gpx3Glutathione peroxidase 31.900.000004-1.140.030NM_007570Btg2aGenes having several probe sets supporting the regulationB-cell translocation gene 2, anti-proliferative1.760.0231.110.535NM_0264331810057C19RikIntegral membrane protein-1.640.00041.090.607NM_008357Il15Interleukin 151.570.00007-1.060.059AI315015Ces3aGenes having several probe sets supporting the regulationCarboxylesterase 31.570.0181.100.513NM_008416JunbJun-B oncogene1.560.043-1.030.864AK011596TfrcTransferrin receptor-1.540.0401.090.315X14678Zfp36aGenes having several probe sets supporting the regulationZinc finger protein 361.490.041-1.030.824BG065702D230025D16RikaGenes having several probe sets supporting the regulationRIKEN cDNA D230025D16 gene1.470.0231.010.823NM_025427RGC-32aGenes having several probe sets supporting the regulationResponse gene to complement 32 (Homo sapiens)1.470.009-1.050.686NM_023065Ifi30Interferon γ-inducible protein 301.460.00007-1.100.094C81193Odc1aGenes having several probe sets supporting the regulationOrnithine decarboxylase, structural 1-1.460.0021.170.052BC010758Cbr2Carbonyl reductase 21.450.003-1.100.179AK0128252810026P18RikRIKEN cDNA 2810026P18 gene-1.450.0161.180.066BC0241189430059P22RikaGenes having several probe sets supporting the regulationTransmembrane protein 46-1.440.0061.160.178U18812LepLeptin-1.430.0191.110.158NM_010858Myl4Myosin, light polypeptide 4-1.430.00021.180.039BB221402CidecCell death-inducing DFFA-like effector c-1.430.0401.200.058BB794641Nos1Nitric-oxide synthase 1, neuronal1.390.00007-1.170.009NM_008452Klf2Kruppel-like factor 21.380.0271.000.968AF378088RhouaGenes having several probe sets supporting the regulationRas homolog gene family, member U1.370.004-1.000.945BM200248Peg3Paternally expressed 3-1.370.015-1.020.790NM_013525Gas5aGenes having several probe sets supporting the regulationGrowth arrest-specific 5-1.360.0041.170.043NM_026524Mid1ip1Mid1 interacting protein 11.340.0041.200.197AJ132394RorcRAR-related orphan receptor gamma1.340.003-1.110.041BC026450Cova1Cytosolic ovarian carcinoma antigen 1-1.340.0061.150.148BB039269Gja1Gap junction membrane channel protein alpha 11.340.030-1.010.873BG069413Klf4Kruppel-like factor 41.330.023-1.030.739BB644164Cugbp2aGenes having several probe sets supporting the regulationCUG triplet repeat, RNA binding protein 2-1.320.0111.080.437BC0124052310001H12RikGonadotropin-regulated transcription factor1.320.0221.040.436BB144704Abca1ATP-binding cassette, sub-family A, member 1-1.320.0061.160.023BM120823Eif4el3Eukaryotic translation initiation factor 4E-like 31.320.004-1.060.485AF176524Fbxl10F-box and leucine-rich repeat protein 10-1.320.0021.130.094BC011116M6prbp1Mannose-6-phosphate receptor binding protein 11.300.013-1.050.327NM_010866Myod1Myogenic differentiation 1-1.300.00091.000.978AI326423Srebf1Sterol regulatory element binding factor 1-1.290.00091.170.014BB475271Luc7l2LUC7-like 2 (S. cerevisiae)-1.290.0381.020.783NM_022019Dusp10Dual specificity phosphatase 10-1.290.0341.180.193BC010564Hist2h2aa1Histone 2, H2aa1-1.290.00071.140.010NM_007394Acvr1Activin A receptor, type 1-1.280.0091.110.122BC025461Tm4sf3Transmembrane 4 superfamily member 31.280.019-1.150.100NM_010761Ccndbp1Cyclin d-type binding protein 11.280.007-1.090.232BC022110Alas1Aminolevulinic acid synthase 11.280.00005-1.090.154BF467211Cdc42Cell division cycle 42 homolog (S. cerevisiae)1.280.001-1.130.036AJ306425HfeHemochromatosis1.270.021-1.170.004NM_009665Amd1S-Adenosylmethionine decarboxylase 1-1.270.0211.080.363NM_008735Nrip1Nuclear receptor interacting protein 1-1.270.0241.000.990NM_015753Zfhx1bZinc finger homeobox 1b-1.270.012-1.060.545NM_0264812700055K07RikCGI-38-1.270.000021.160.108BC015254Cmkor1Chemokine orphan receptor 11.270.022-1.060.567NM_020604Jph1Junctophilin 1-1.260.0191.050.663BF577544Pole4Polymerase epsilon 4-1.260.0211.040.375NM_009523Wnt4Wingless-related MMTV integration site 4-1.260.00011.130.018BB114336Bace1β-Site APP cleaving enzyme 1-1.260.0361.040.550AK004781Sox17SRY-box containing gene 171.260.003-1.010.950BC014718Dnase1Deoxyribonuclease I-1.250.0011.160.115AW9889811110008H02RikRIKEN cDNA 1110008H02 gene-1.250.0061.190.166NM_011430SncgSynuclein, gamma-1.250.0211.030.638NM_010240Ftl1Ferritin light chain 11.250.0151.000.959BC009165ThrspThyroid hormone-responsive SPOT14 homolog (Rattus)1.250.0271.010.931NM_008393Irx3Iroquois-related homeobox 3 (Drosophila)1.250.0121.000.953NM_009379ThpoThrombopoietin1.250.004-1.110.024NM_008258Hn1Hematological and neurological expressed sequence 11.250.0091.020.782BG070255Pde7aaGenes having several probe sets supporting the regulationPhosphodiesterase 7A1.250.028-1.100.141NM_015797Fbxo6bF-box only protein 6b1.240.010-1.070.080BC010712Cri1CREBBP/EP300 inhibitory protein 1-1.240.026-1.020.763BB261602Map2k6Mitogen-activated protein kinase kinase 61.240.030-1.070.107U43884Idb1Inhibitor of DNA binding 11.240.033-1.050.473BB2782861810073P09RikmKIAA17601.240.013-1.020.659AK004847Rnf128aGenes having several probe sets supporting the regulationRing finger protein 1281.240.015-1.070.176AK0186054631408O11RikRIKEN cDNA 4631408O11 gene-1.240.039-1.010.883BB039247C1qr1Complement component 1, q subcomponent, receptor 11.240.0071.000.991AV276428BC043118cDNA sequence BC0431181.240.002-1.100.036AK018482Fbxo9F-box only protein 9-1.240.0311.010.866BB066232Catna1Catenin α 11.240.0471.010.913BI143942Sdh1aGenes having several probe sets supporting the regulationSorbitol dehydrogenase 11.240.0007-1.010.903BB3590431700007D05RikTranscription termination factor-like protein1.230.016-1.090.060BC021914MmdMonocyte to macrophage differentiation-associated-1.230.0421.000.983AK020120Hrmt1l2Heterogeneous nuclear ribonucleoproteins methyltransferase-like 2 (S. cerevisiae)-1.230.0431.100.652AK010029Oxct1aGenes having several probe sets supporting the regulation3-Oxoacid-CoA transferase 11.230.001-1.100.024BM935811Itga6Integrin α 61.230.0161.020.786BB8187024933439F18RikRIKEN cDNA 4933439F18 gene-1.230.0151.070.069BE986849Ppp1r14bProtein phosphatase 1, regulatory subunit 14B-1.230.000021.110.005BB1451011110028E10RikCholine transporter-like properties-1.230.0031.090.221BC019757Hist1h4iHistone 1, H4i-1.220.0161.120.231AV336908DlatDihydrolipoamide S-acetyltransferase1.220.019-1.120.080AB031049Rev3lREV3-like-1.220.0021.050.569BB033733Trim16Tripartite motif protein 161.220.021-1.020.565AB032010Fxyd6FXYD domain-containing ion transport regulator 6-1.220.020-1.040.362NM_009214SmsSpermine synthase-1.220.0261.100.199AW543698Cdh5Cadherin 51.220.009-1.040.299BC023112Galnact2Chondroitin sulfate GalNAcT-2-1.210.0411.130.058NM_024439H47Histocompatibility 47-1.210.0261.140.022NM_020581Angptl4Angiopoietin-like 4-1.210.0111.050.287AF289490AsphaGenes having several probe sets supporting the regulationAspartate-β-hydroxylase-1.210.0231.180.001BC008105PolkPolymerase, kappa-1.210.00051.080.166NM_018832PdzxPDZ domain containing, X chromosome1.210.016-1.050.328AF276917Glrx1Glutaredoxin 1 (thioltransferase)1.210.018-1.170.016NM_007472Aqp1Aquaporin 11.210.010-1.040.294AW741459Eif4bEukaryotic translation initiation factor 4B-1.210.0051.070.130NM_009076Rpl12Ribosomal protein L12-1.210.0151.100.224C78422Coq3Coenzyme Q3 homolog, methyltransferase (yeast)1.210.013-1.080.036BI739053Clcn3Chloride channel 31.210.039-1.020.866NM_008173Nr3c1Nuclear receptor subfamily 3, group C, member 1-1.210.0091.140.191NM_022310Hspa5Heat shock 70-kDa protein 5 (glucose-regulated protein)-1.210.0071.140.024BG801851Actr1bARP1 actin-related protein 1 homolog B (yeast)1.200.0401.010.946AW989410Pbef1Pre-B-cell colony-enhancing factor 11.200.005-1.130.016NM_138953Ell2Elongation factor RNA polymerase II 2-1.200.0231.150.297BB667778Neo1Neogenin-1.200.000031.080.043NM_010437Hivep2Human immunodeficiency virus type I enhancer binding protein 2-1.200.027-1.010.877NM_016959Rps3aRibosomal protein S3a-1.200.000091.060.067NM_007508Atp6v1a1ATPase, H+ transporting, V1 subunit A, isoform 11.200.002-1.010.894BC022959Acsl6Acyl-CoA synthetase long-chain family member 61.200.025-1.010.735AK0033505730454B08RikZinc finger CCCH-type domain containing 11A-1.200.0071.060.067BC003451Mat2aMethionine adenosyltransferase II, α-1.200.0371.150.225Genes differentially expressed in Prkag3-/- compared with wild-type littermatesNM_021537Stk25Serine/threonine kinase 25 (yeast)-1.000.913-1.880.00003AK009959Ankrd1aGenes having several probe sets supporting the regulationAnkyrin repeat domain 11.230.141-1.480.030D87867Ugt1a12aGenes having several probe sets supporting the regulationUDP-glycosyltransferase 1 family polypeptide members A12, A10, A5, A6, A1, and A2-1.100.3281.420.009AK009828Neu2Neuraminidase 21.170.002-1.420.000004BC019124Lmcd1LIM and cysteine-rich domains 11.090.356-1.400.010AV152334Atp1b1aGenes having several probe sets supporting the regulationATPase, Na+/K+ transporting, β1 polypeptide-1.140.395-1.370.004NM_009208Slc4a3Solute carrier family 4, member 3-1.040.6531.340.010BB534670Cd36CD36 antigen1.080.658-1.330.008AJ288061Clasp1CLIP associating protein 11.000.9351.320.006NM_024264Cyp27a1Cytochrome P450, family 27, subfamily a, polypeptide 1-1.170.1021.300.001AK004757Stk11ipSerine/threonine kinase 11 interacting protein1.020.815-1.290.00003AK007410Gadd45gGrowth arrest and DNA-damage-inducible 45γ-1.130.6171.270.010NM_016894Ramp1Receptor activity modifying protein 11.020.780-1.260.005NM_013626PamPeptidylglycine α-amidating monooxygenase-1.040.2721.260.001NM_013750Phlda3Pleckstrin homology-like domain, family A, member 31.160.003-1.250.026BM207588Slc2a1Solute carrier family 2 (facilitated glucose transporter), member 1-1.130.2031.250.022BB0856042610031L17Rikputative mitochondrial outer membrane" @default.
• W2010284467 created "2016-06-24" @default.
• W2010284467 creator A5000008605 @default.
• W2010284467 creator A5001825767 @default.
• W2010284467 creator A5031206416 @default.
• W2010284467 creator A5036276290 @default.
• W2010284467 creator A5041424157 @default.
• W2010284467 creator A5041656388 @default.
• W2010284467 creator A5044651065 @default.
• W2010284467 creator A5050285122 @default.
• W2010284467 creator A5058411284 @default.
• W2010284467 date "2006-03-01" @default.
• W2010284467 modified "2023-10-02" @default.
• W2010284467 title "Opposite Transcriptional Regulation in Skeletal Muscle of AMP-activated Protein Kinase γ3 R225Q Transgenic Versus Knock-out Mice" @default.
• W2010284467 cites W1543440244 @default.
• W2010284467 cites W1860680701 @default.
• W2010284467 cites W1883802169 @default.
• W2010284467 cites W1959374451 @default.
• W2010284467 cites W1964100540 @default.
• W2010284467 cites W1971082641 @default.
• W2010284467 cites W1973123665 @default.
• W2010284467 cites W1984966905 @default.
• W2010284467 cites W1986704854 @default.
• W2010284467 cites W1996105881 @default.
• W2010284467 cites W1997085985 @default.
• W2010284467 cites W2014715754 @default.
• W2010284467 cites W2015511075 @default.
• W2010284467 cites W2022276077 @default.
• W2010284467 cites W2025435739 @default.
• W2010284467 cites W2027815803 @default.
• W2010284467 cites W2033663584 @default.
• W2010284467 cites W2049702067 @default.
• W2010284467 cites W2053188966 @default.
• W2010284467 cites W2059155059 @default.
• W2010284467 cites W2059825898 @default.
• W2010284467 cites W2067979493 @default.
• W2010284467 cites W2069512653 @default.
• W2010284467 cites W2072314593 @default.
• W2010284467 cites W2073181999 @default.
• W2010284467 cites W2074303577 @default.
• W2010284467 cites W2077230920 @default.
• W2010284467 cites W2089025383 @default.
• W2010284467 cites W2095454212 @default.
• W2010284467 cites W2105945237 @default.
• W2010284467 cites W2113513414 @default.
• W2010284467 cites W2123397214 @default.
• W2010284467 cites W2130344015 @default.
• W2010284467 cites W2135424721 @default.
• W2010284467 cites W2135817715 @default.
• W2010284467 cites W2136699926 @default.
• W2010284467 cites W2140586775 @default.
• W2010284467 cites W2147553969 @default.
• W2010284467 cites W2149785020 @default.
• W2010284467 cites W2151359455 @default.
• W2010284467 cites W2152791345 @default.
• W2010284467 cites W2154405414 @default.
• W2010284467 cites W2156518233 @default.
• W2010284467 cites W2157560347 @default.
• W2010284467 cites W2159620999 @default.
• W2010284467 cites W2166527628 @default.
• W2010284467 cites W2166714586 @default.
• W2010284467 cites W2234536545 @default.
• W2010284467 cites W352932046 @default.
• W2010284467 cites W4230496537 @default.
• W2010284467 doi "https://doi.org/10.1074/jbc.m510461200" @default.
• W2010284467 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16410251" @default.
• W2010284467 hasPublicationYear "2006" @default.
• W2010284467 type Work @default.
• W2010284467 sameAs 2010284467 @default.
• W2010284467 citedByCount "61" @default.
• W2010284467 countsByYear W20102844672012 @default.
• W2010284467 countsByYear W20102844672013 @default.
• W2010284467 countsByYear W20102844672014 @default.
• W2010284467 countsByYear W20102844672015 @default.
• W2010284467 countsByYear W20102844672016 @default.
• W2010284467 countsByYear W20102844672017 @default.
• W2010284467 countsByYear W20102844672018 @default.
• W2010284467 countsByYear W20102844672020 @default.
• W2010284467 countsByYear W20102844672021 @default.
• W2010284467 countsByYear W20102844672022 @default.
• W2010284467 countsByYear W20102844672023 @default.
• W2010284467 crossrefType "journal-article" @default.
• W2010284467 hasAuthorship W2010284467A5000008605 @default.
• W2010284467 hasAuthorship W2010284467A5001825767 @default.
• W2010284467 hasAuthorship W2010284467A5031206416 @default.
• W2010284467 hasAuthorship W2010284467A5036276290 @default.
• W2010284467 hasAuthorship W2010284467A5041424157 @default.
• W2010284467 hasAuthorship W2010284467A5041656388 @default.
• W2010284467 hasAuthorship W2010284467A5044651065 @default.
• W2010284467 hasAuthorship W2010284467A5050285122 @default.
• W2010284467 hasAuthorship W2010284467A5058411284 @default.
• W2010284467 hasBestOaLocation W20102844671 @default.
• W2010284467 hasConcept C102230213 @default.
• W2010284467 hasConcept C104317684 @default.
• W2010284467 hasConcept C134018914 @default.
• W2010284467 hasConcept C141035611 @default.
• W2010284467 hasConcept C153911025 @default.
• W2010284467 hasConcept C182704531 @default.

• next