Thr183
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Home > Phosphorylation Site Page: > Thr183  -  AMPKA1 (rat)

Site Information
SDGEFLRtsCGSPNY   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448786

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 48 , 55 ) , electrophoretic mobility shift ( 53 ) , immunoprecipitation ( 1 , 8 ) , mass spectrometry ( 6 , 48 ) , mass spectrometry (in vitro) ( 3 ) , microscopy-colocalization with upstream kinase ( 1 ) , mutation of modification site ( 32 , 42 , 48 , 54 , 55 ) , phospho-antibody ( 1 , 2 , 4 , 5 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 16 , 17 , 18 , 19 , 20 , 22 , 23 , 24 , 25 , 26 , 27 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 43 , 44 , 45 , 47 , 48 , 50 , 51 , 52 , 53 ) , western blotting ( 1 , 2 , 4 , 5 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 16 , 17 , 19 , 20 , 23 , 24 , 25 , 26 , 27 , 29 , 31 , 32 , 33 , 34 , 35 , 36 , 38 , 40 , 45 , 51 , 52 , 53 )
Disease tissue studied:
breast cancer ( 19 ) , kidney cancer ( 10 ) , liver cancer ( 19 , 38 , 51 ) , pancreatic cancer ( 20 , 32 ) , pancreatic carcinoma ( 20 , 32 ) , diabetes mellitus ( 30 ) , type 2 diabetes ( 30 )
Relevant cell line - cell type - tissue:
'muscle, skeletal' ( 2 , 4 , 7 , 11 , 16 , 17 , 24 , 30 , 33 , 45 , 50 , 52 ) , 'muscle, smooth'-thoracic aorta ( 18 ) , 293 (epithelial) ( 42 ) , 3T3-L1 (fibroblast) ( 25 , 38 ) , adipose tissue ( 13 , 27 ) , astrocyte ( 44 ) , C2C12 (myoblast) ( 25 ) , Chang liver (cervical) [AMPKB1 (rat)] ( 54 ) , Chang liver (cervical) [AMPKG1 (rat)] ( 54 ) , Chang liver (cervical) ( 48 ) , Clone 9 (hepatic) ( 53 ) , COS (fibroblast) ( 32 , 55 ) , ELT-3 ( 10 ) , granulosa ( 39 ) , H4IIe (hepatic) ( 51 ) , heart ( 23 , 36 , 47 ) , hepatocyte-liver ( 14 , 40 ) , HepG2 (hepatic) ( 38 ) , HIT-T15 (pancreatic) ( 41 ) , IEC-18 (epithelial) ( 26 ) , INS-1 (pancreatic) ( 20 , 32 ) , kidney ( 10 , 22 ) , L6 (myoblast) ( 25 , 34 , 37 , 38 ) , liver ( 5 , 6 , 19 , 31 ) , mammary gland ( 19 ) , MEF (fibroblast) ( 32 ) , MMDD1 (renal) ( 22 ) , muscle ( 12 ) , myocyte-heart ( 9 , 29 , 35 , 43 , 47 ) , RIN (epithelial) ( 41 ) , vessel ( 30 )

Upstream Regulation
Regulatory protein:
Akt1 (rat) ( 35 ) , CAB39 (human) ( 29 ) , CAMK2A (human) ( 1 ) , LKB1 (human) ( 35 ) , LKB1 (mouse) ( 29 ) , LKB1 (rat) ( 1 ) , STRAD (human) ( 29 )
Putative in vivo kinases:
AMPKA1 (rat) ( 55 ) , CAMK2B (rat) ( 18 ) , CAMKK2 (mouse) ( 32 )
Kinases, in vitro:
AMPKA1 (rat) ( 21 ) , CAMKK1 (rat) ( 28 , 32 ) , CAMKK2 (human) ( 15 ) , CAMKK2 (rat) ( 32 ) , LKB1 (human) ( 28 , 36 , 46 , 49 ) , LKB1 (mouse) ( 48 , 56 )
Putative upstream phosphatases:
PPP2R2D (human) ( 1 )
Phosphatases, in vitro:
PPP2CA (rat) ( 15 , 28 )
Treatments:
2-deoxyglucose ( 38 ) , 8-Br-AMP ( 31 ) , A23187 ( 18 ) , acadesine ( 7 , 17 , 25 , 31 , 33 , 37 , 39 , 40 , 43 , 53 ) , adiponectin ( 14 , 45 , 50 ) , angiotensin_2 ( 9 , 18 ) , anoxia ( 48 ) , berberine ( 7 ) , caffeine ( 4 , 24 ) , calyculin_A ( 40 ) , cantharidin ( 40 ) , colforsin ( 14 , 20 , 32 ) , compound_C ( 10 , 13 , 16 , 20 ) , cyanide ( 44 ) , DNP ( 7 ) , EGTA ( 18 ) , electrical_stimulation ( 12 ) , endothelin ( 18 ) , exercise ( 12 , 17 , 27 , 52 ) , exercise training ( 52 ) , fasting ( 11 ) , food deprivation ( 19 ) , FPPF ( 20 ) , GIP ( 20 ) , glucose ( 38 ) , H-89 ( 20 ) , heat_shock ( 8 ) , hypoxia ( 35 ) , IGF-1 ( 39 ) , insulin ( 2 , 11 , 12 , 36 , 38 , 47 ) , Intralipid ( 43 ) , ischemia ( 36 ) , L-NAME ( 43 ) , leptin ( 41 ) , linoleic_acid ( 34 ) , liothyronine ( 9 , 16 ) , metformin ( 7 , 23 , 38 , 47 , 51 ) , microcystin-LR ( 40 ) , midazolam ( 31 ) , muscle contraction ( 2 , 11 ) , naringin ( 40 ) , nicotinamide ( 16 ) , nitric_oxide ( 44 ) , okadaic_acid ( 1 , 40 ) , oligomycin ( 44 , 51 ) , osmotic_stress ( 48 ) , palmitate ( 34 ) , phenformin ( 23 ) , phenobarbital ( 31 ) , prazosin ( 13 ) , propranolol ( 13 ) , racepinefrine ( 27 , 37 ) , refeeding ( 11 ) , rosiglitazone ( 5 , 14 ) , serum ( 12 ) , sodium_azide ( 55 ) , STO-609 ( 1 , 18 ) , tautomycin ( 26 , 40 ) , urofollitropin ( 39 ) , vasopressin ( 18 ) , wortmannin ( 16 , 32 )

Downstream Regulation
Effects of modification on AMPKA1:
enzymatic activity, induced ( 27 , 28 , 30 , 31 , 48 , 50 , 54 , 55 ) , molecular association, regulation ( 10 ) , protein stabilization ( 10 )
Induce interaction with:
14-3-3 beta (human) ( 10 ) , 14-3-3 epsilon (human) ( 10 ) , 14-3-3 eta (human) ( 10 ) , 14-3-3 gamma (human) ( 10 ) , 14-3-3 sigma (human) ( 10 ) , 14-3-3 theta (human) ( 10 ) , 14-3-3 zeta (human) ( 10 )

Disease / Diagnostics Relevance
Relevant diseases:
hypertrophic cardiomyopathy ( 9 ) , type 2 diabetes ( 30 )

References 

1

Joseph BK, et al. (2015) Inhibition of AMP Kinase by the Protein Phosphatase 2A Heterotrimer, PP2APpp2r2d. J Biol Chem 290, 10588-98
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2

Lin FC, et al. (2012) Effect of insulin and contraction on glycogen synthase phosphorylation and kinetic properties in epitrochlearis muscles from lean and obese Zucker rats. Am J Physiol Cell Physiol 302, C1539-47
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3

Löffler AS, et al. (2011) Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop. Autophagy 7, 696-706
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4

Egawa T, et al. (2011) Caffeine activates preferentially α1-isoform of 5'AMP-activated protein kinase in rat skeletal muscle. Acta Physiol (Oxf) 201, 227-38
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5

Yang SJ, et al. (2011) Activation of peroxisome proliferator-activated receptor gamma by rosiglitazone increases sirt6 expression and ameliorates hepatic steatosis in rats. PLoS One 6, e17057
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6

Demirkan G, et al. (2011) Phosphoproteomic Profiling of In Vivo Signaling in Liver by the Mammalian Target of Rapamycin Complex 1 (mTORC1). PLoS One 6, e21729
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7

Ma X, et al. (2010) Berberine-induced activation of 5'-adenosine monophosphate-activated protein kinase and glucose transport in rat skeletal muscles. Metabolism 59, 1619-27
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8

Kazgan N, Williams T, Forsberg LJ, Brenman JE (2010) Identification of a nuclear export signal in the catalytic subunit of AMP-activated protein kinase. Mol Biol Cell 21, 3433-42
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9

Jiang SY, et al. (2010) A distinct AMP-activated protein kinase phosphorylation site characterizes cardiac hypertrophy induced by L-thyroxine and angiotensin II. Clin Exp Pharmacol Physiol 37, 919-25
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10

Short JD, et al. (2010) AMPK-mediated phosphorylation of murine p27 at T197 promotes binding of 14-3-3 proteins and increases p27 stability. Mol Carcinog 49, 429-39
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11

Lai YC, Zarrinpashneh E, Jensen J (2010) Additive effect of contraction and insulin on glucose uptake and glycogen synthase in muscle with different glycogen contents. J Appl Physiol 108, 1106-15
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12

Funai K, et al. (2010) In vivo exercise followed by in vitro contraction additively elevates subsequent insulin-stimulated glucose transport by rat skeletal muscle. Am J Physiol Endocrinol Metab 298, E999-1010
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13

Hattori A, et al. (2010) Beta-adrenergic-AMPK pathway phosphorylates acetyl-CoA carboxylase in a high-epinephrine rat model, SPORTS. Obesity (Silver Spring) 18, 48-54
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14

Yoon YS, et al. (2009) Adiponectin and thiazolidinedione targets CRTC2 to regulate hepatic gluconeogenesis. Exp Mol Med 41, 577-83
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15

McBride A, Ghilagaber S, Nikolaev A, Hardie DG (2009) The glycogen-binding domain on the AMPK beta subunit allows the kinase to act as a glycogen sensor. Cell Metab 9, 23-34
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16

de Lange P, et al. (2008) Rapid activation by 3,5,3'-L-triiodothyronine of adenosine 5'-monophosphate-activated protein kinase/acetyl-coenzyme a carboxylase and akt/protein kinase B signaling pathways: relation to changes in fuel metabolism and myosin heavy-chain protein content in rat gastrocnemius muscle in vivo. Endocrinology 149, 6462-70
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17

McConell GK, et al. (2008) Differential attenuation of AMPK activation during acute exercise following exercise training or AICAR treatment. J Appl Physiol 105, 1422-7
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18

Horman S, et al. (2008) AMP-activated protein kinase phosphorylates and desensitizes smooth muscle myosin light chain kinase. J Biol Chem 283, 18505-12
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19

Jiang W, Zhu Z, Thompson HJ (2008) Dietary energy restriction modulates the activity of AMP-activated protein kinase, Akt, and mammalian target of rapamycin in mammary carcinomas, mammary gland, and liver. Cancer Res 68, 5492-9
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20

Kim SJ, Nian C, Widenmaier S, McIntosh CH (2008) Glucose-dependent insulinotropic polypeptide-mediated up-regulation of beta-cell antiapoptotic Bcl-2 gene expression is coordinated by cyclic AMP (cAMP) response element binding protein (CREB) and cAMP-responsive CREB coactivator 2. Mol Cell Biol 28, 1644-56
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21

Sanders MJ, et al. (2007) Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family. J Biol Chem 282, 32539-48
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22

Fraser SA, et al. (2007) Regulation of the renal-specific Na+-K+-2Cl- co-transporter NKCC2 by AMP-activated protein kinase (AMPK). Biochem J 405, 85-93
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23

Zhang L, He H, Balschi JA (2007) Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration. Am J Physiol Heart Circ Physiol 293, H457-66
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24

Jensen TE, et al. (2007) Caffeine-induced Ca(2+) release increases AMPK-dependent glucose uptake in rodent soleus muscle. Am J Physiol Endocrinol Metab 293, E286-92
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25

Suzuki A, et al. (2007) Leptin stimulates fatty acid oxidation and peroxisome proliferator-activated receptor alpha gene expression in mouse C2C12 myoblasts by changing the subcellular localization of the alpha2 form of AMP-activated protein kinase. Mol Cell Biol 27, 4317-27
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26

Guan L, et al. (2007) Protein kinase C-mediated down-regulation of cyclin D1 involves activation of the translational repressor 4E-BP1 via a phosphoinositide 3-kinase/Akt-independent, protein phosphatase 2A-dependent mechanism in intestinal epithelial cells. J Biol Chem 282, 14213-25
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27

Koh HJ, et al. (2007) Adrenaline is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes. Biochem J 403, 473-81
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28

Sanders MJ, et al. (2007) Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade. Biochem J 403, 139-48
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29

Noga AA, et al. (2007) Expression of an active LKB1 complex in cardiac myocytes results in decreased protein synthesis associated with phenylephrine-induced hypertrophy. Am J Physiol Heart Circ Physiol 292, H1460-9
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30

Blume C, et al. (2007) AMP-activated protein kinase impairs endothelial actin cytoskeleton assembly by phosphorylating vasodilator-stimulated phosphoprotein. J Biol Chem 282, 4601-12
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31

Shindo S, Numazawa S, Yoshida T (2007) A physiological role of AMP-activated protein kinase in phenobarbital-mediated constitutive androstane receptor activation and CYP2B induction. Biochem J 401, 735-41
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32

Hurley RL, et al. (2006) Regulation of AMP-activated protein kinase by multisite phosphorylation in response to agents that elevate cellular cAMP. J Biol Chem 281, 36662-72
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33

Fediuc S, Gaidhu MP, Ceddia RB (2006) Inhibition of insulin-stimulated glycogen synthesis by 5-aminoimidasole-4-carboxamide-1-beta-d-ribofuranoside-induced adenosine 5'-monophosphate-activated protein kinase activation: interactions with Akt, glycogen synthase kinase 3-3alpha/beta, and glycogen synthase in isolated rat soleus muscle. Endocrinology 147, 5170-7
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34

Watt MJ, et al. (2006) Fatty acids stimulate AMP-activated protein kinase and enhance fatty acid oxidation in L6 myotubes. J Physiol 574, 139-47
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35

Soltys CL, Kovacic S, Dyck JR (2006) Activation of cardiac AMP-activated protein kinase by LKB1 expression or chemical hypoxia is blunted by increased Akt activity. Am J Physiol Heart Circ Physiol 290, H2472-9
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36

Horman S, et al. (2006) Insulin antagonizes ischemia-induced Thr172 phosphorylation of AMP-activated protein kinase alpha-subunits in heart via hierarchical phosphorylation of Ser485/491. J Biol Chem 281, 5335-40
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37

Watt MJ, et al. (2006) Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue. Am J Physiol Endocrinol Metab 290, E500-8
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38

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39

Tosca L, et al. (2005) Adenosine 5'-monophosphate-activated protein kinase regulates progesterone secretion in rat granulosa cells. Endocrinology 146, 4500-13
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40

Samari HR, et al. (2005) Stimulation of hepatocytic AMP-activated protein kinase by okadaic acid and other autophagy-suppressive toxins. Biochem J 386, 237-44
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41

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42

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43

Shearer J, et al. (2004) AMPK stimulation increases LCFA but not glucose clearance in cardiac muscle in vivo. Am J Physiol Endocrinol Metab 287, E871-7
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44

Almeida A, Moncada S, Bolaños JP (2004) Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway. Nat Cell Biol 6, 45-51
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45

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46

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47

Kovacic S, et al. (2003) Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart. J Biol Chem 278, 39422-7
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48

Woods A, et al. (2003) Identification of phosphorylation sites in AMP-activated protein kinase (AMPK) for upstream AMPK kinases and study of their roles by site-directed mutagenesis. J Biol Chem 278, 28434-42
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49

Hawley SA, et al. (2003) Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol 2, 28
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50

Tomas E, et al. (2002) Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci U S A 99, 16309-13
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51

Hawley SA, Gadalla AE, Olsen GS, Hardie DG (2002) The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes 51, 2420-5
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52

Durante PE, et al. (2002) Effects of endurance training on activity and expression of AMP-activated protein kinase isoforms in rat muscles. Am J Physiol Endocrinol Metab 283, E178-86
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53

Abbud W, et al. (2000) Stimulation of AMP-activated protein kinase (AMPK) is associated with enhancement of Glut1-mediated glucose transport. Arch Biochem Biophys 380, 347-52
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54

Stein SC, et al. (2000) The regulation of AMP-activated protein kinase by phosphorylation. Biochem J 345 Pt 3, 437-43
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55

Mitchelhill KI, et al. (1997) Posttranslational modifications of the 5'-AMP-activated protein kinase beta1 subunit. J Biol Chem 272, 24475-9
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56

Hawley SA, 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, 27879-87
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