Thr308
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Site Information
KDGAtMKtFCGtPEy   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447856

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 92 , 159 , 168 ) , flow cytometry ( 9 , 74 ) , immunoprecipitation ( 6 , 9 , 20 , 41 , 84 , 170 ) , mass spectrometry ( 10 , 12 , 33 , 35 ) , mutation of modification site ( 41 , 64 , 130 , 136 , 139 , 159 , 161 , 162 , 170 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 14 , 16 , 17 , 18 , 19 , 20 , 21 , 23 , 24 , 26 , 29 , 31 , 34 , 37 , 39 , 41 , 44 , 46 , 47 , 48 , 50 , 51 , 52 , 53 , 54 , 55 , 57 , 58 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 68 , 69 , 70 , 71 , 72 , 73 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 148 , 149 , 150 , 151 , 153 , 154 , 155 , 156 , 157 , 158 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 ) , phosphoamino acid analysis ( 107 ) , phosphopeptide mapping ( 168 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 14 , 16 , 18 , 19 , 20 , 21 , 23 , 24 , 26 , 29 , 31 , 34 , 37 , 39 , 41 , 44 , 46 , 47 , 48 , 50 , 51 , 52 , 53 , 54 , 55 , 57 , 61 , 62 , 63 , 64 , 65 , 66 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 112 , 113 , 114 , 115 , 117 , 118 , 119 , 120 , 121 , 128 , 129 , 131 , 134 , 135 , 136 , 138 , 139 , 141 , 145 , 148 , 150 , 151 , 154 , 156 , 157 , 158 , 160 , 161 , 166 , 167 , 168 , 169 , 170 )
Disease tissue studied:
bone cancer ( 47 ) , breast cancer ( 8 , 58 , 167 ) , breast adenocarcinoma ( 58 ) , colorectal cancer ( 47 , 64 ) , colorectal carcinoma ( 47 , 64 ) , liver cancer ( 15 , 93 ) , hepatocellular carcinoma ( 15 ) , lung cancer ( 64 ) , non-small cell lung cancer ( 64 ) , neuroblastoma ( 10 , 154 ) , pancreatic cancer ( 64 ) , pancreatic carcinoma ( 64 ) , multiple myeloma ( 150 ) , fibrosarcoma of soft tissue ( 150 , 161 ) , schizophrenia ( 141 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 18 ) , 'brain, cerebral cortex' ( 117 , 141 ) , 'brain, embryonic' [BAG1 (mouse)] ( 124 ) , 'brain, hippocampus' ( 73 , 117 ) , 'brain, nucleus accumbens' ( 11 ) , 'brain, striatum' ( 117 , 126 ) , 'muscle, skeletal' ( 1 , 51 , 66 , 85 , 89 , 97 , 98 , 103 , 110 , 111 , 134 , 144 ) , 'muscle, skeletal' [CAMKK1 (mouse)] ( 104 ) , 'muscle, skeletal' [DNAPK (mouse), homozygous knockout] ( 94 ) , 'muscle, skeletal' [RICTOR (mouse), homozygous knockout] ( 83 , 100 ) , 'neuron, cortical' ( 37 ) , 'neuron, cortical'-brain ( 10 , 151 , 153 ) , 'neuron, hippocampal' ( 37 ) , 'neuron, superior cervical ganglion' ( 96 ) , 'renal, podocyte' ( 63 ) , 'stem, embryonic' ( 97 ) , 293 (epithelial) ( 6 , 72 , 76 , 119 , 146 , 162 , 168 , 170 ) , 293T (epithelial) ( 84 , 157 , 169 ) , 3T3 (fibroblast) ( 65 , 79 , 80 , 87 , 107 , 158 ) , 3T3 (fibroblast) [INSR (human)] ( 168 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 128 , 130 , 132 , 155 , 156 , 160 , 162 , 163 , 165 ) , 3T3-L1 (fibroblast) ( 75 , 120 ) , 4T1 (breast cell) ( 167 ) , A431 (epithelial) ( 64 ) , A549 (pulmonary) ( 64 ) , adipocyte ( 108 ) , adipose tissue ( 31 , 97 , 129 ) , adipose tissue [DNAPK (mouse), homozygous knockout] ( 94 ) , adipose tissue [RICTOR (mouse), homozygous knockout] ( 83 ) , AV12 ('neuron, neostriatal') ( 135 ) , B lymphocyte [BCAP (mouse), homozygous knockout] ( 99 ) , B lymphocyte [CD19 (mouse), homozygous knockout] ( 99 ) , B lymphocyte-spleen ( 69 ) , B9 (fibroblast) ( 150 ) , BJMC3879luc2 ( 58 ) , BLMVEC (endothelial) ( 139 ) , BMMC (mast) ( 57 ) , brain ( 29 , 35 , 115 ) , breast [PDK1 (mouse), homozygous knockout] ( 8 ) , C141 (epidermal) ( 159 ) , C2C12 (myoblast) ( 44 , 82 , 92 , 105 ) , C2C12 (myoblast) [LIN28A (mouse), transfection] ( 46 ) , CHO (fibroblast) [EphB1 (human), transfection] ( 166 ) , CHO (fibroblast) [Tau iso8 (human)] ( 114 ) , COS (fibroblast) ( 142 , 149 , 162 ) , CTL-EN (T lymphocyte) ( 101 ) , DLD1 (intestinal) ( 64 ) , E14tg2a ('stem, embryonic') ( 131 ) , embryo ( 35 ) , endothelial-aorta ( 137 ) , epithelial ( 70 ) , epithelial [PIK3R1 (mouse), homozygous knockout] ( 60 ) , ES (stem) ( 19 , 138 ) , fibroblast ( 4 ) , fibroblast-embryo [BAG1 (mouse)] ( 124 ) , GD25 (fibroblast) ( 148 ) , HaCaT (keratinocyte) ( 5 ) , HCCLM3 (hepatic) ( 15 ) , HCT116 (intestinal) ( 47 ) , HCT15 (intestinal) ( 64 ) , heart ( 33 , 97 , 102 , 143 ) , heart [DNAPK (human), transfection] ( 94 ) , heart [PDHK4 (mouse), homozygous knockout] ( 34 ) , HeLa (cervical) ( 41 , 47 , 54 , 64 , 142 ) , hepatocyte-liver ( 93 ) , hepatocyte-liver [TSC1 (mouse), homozygous knockout] ( 50 ) , HepG2 (hepatic) ( 93 , 170 ) , HT-22 (neuron) ( 153 ) , HT-4 (neuron) ( 153 ) , HUVEC (endothelial) ( 108 ) , JB (epithelial) ( 164 ) , keratinocyte ( 118 ) , keratinocyte-skin ( 116 ) , keratinocyte-skin [IGF1 (mouse)] ( 119 ) , L6 (myoblast) ( 65 ) , liver ( 31 , 35 , 55 , 77 , 97 , 121 , 134 ) , liver [DNAPK (mouse), homozygous knockout] ( 94 ) , liver [RICTOR (mouse), homozygous knockout] ( 83 ) , lymphocyte ( 9 , 12 , 141 ) , lymphocyte-spleen ( 3 , 14 ) , macrophage-bone marrow ( 7 , 106 , 145 ) , mast-bone marrow ( 130 ) , MEF (fibroblast) ( 6 , 17 , 31 , 39 , 53 , 54 , 68 , 72 , 76 , 91 , 92 , 109 , 112 , 113 ) , MEF (fibroblast) [BAG4 (mouse), homozygous knockout] ( 48 ) , MEF (fibroblast) [DEDD (mouse), homozygous knockout] ( 88 ) , MEF (fibroblast) [DNAPK (mouse), homozygous knockout] ( 94 ) , MEF (fibroblast) [IGF1R (mouse)] ( 122 , 127 ) , MEF (fibroblast) [Sin1 (mouse), homozygous knockout] ( 90 ) , MEF (fibroblast) [TMEM55B (mouse), homozygous knockout] ( 86 ) , MHCC97-L (hepatic) ( 15 ) , MIA PaCa-2 (pancreatic) ( 64 ) , MLO-Y4 (osteoblast) ( 29 ) , MPC-11 (B lymphocyte) ( 150 ) , myeloid ( 106 ) , myoblast ( 98 , 136 ) , myocyte-heart ( 24 , 52 ) , N1E-115 (neuron) ( 10 ) , NCI-H1299 (pulmonary) ( 64 ) , Neuro-2a (neuron) ( 154 ) , neutrophil ( 26 ) , NMuMG (epithelial) ( 20 , 167 ) , osteoclast ( 106 ) , pancreas ( 88 ) , PaTu (pancreatic) ( 64 ) , PC3 (prostate cell) ( 162 ) , placenta ( 16 ) , platelet-blood ( 2 , 140 ) , preadipocyte ( 108 ) , prostate ( 78 ) , SF9 ( 163 ) , skin ( 5 , 133 ) , Swiss 3T3 (fibroblast) ( 157 ) , SYF (fibroblast) ( 62 ) , T lymphocyte ( 74 ) , T lymphocyte-blood ( 81 ) , T lymphocyte-lymph node [PKCT (mouse), homozygous knockout] ( 61 ) , T lymphocyte-spleen [PKCT (mouse), homozygous knockout] ( 61 ) , U2OS (bone cell) ( 47 ) , uterus ( 125 ) , WEHI-164 (fibroblast) ( 161 )

Upstream Regulation
Regulatory protein:
14-3-3 zeta (mouse) ( 84 ) , Akt2 (mouse) ( 110 ) , ASK1 (human) ( 76 ) , ASK1 (mouse) ( 76 ) , BAG1 (mouse) ( 124 ) , BAG4 (mouse) ( 48 ) , BCAP (mouse) ( 99 ) , Brk (human) ( 62 ) , CAMKK1 (mouse) ( 104 ) , CD19 (mouse) ( 99 ) , CDC42 iso1 (human) ( 107 ) , DICER1 (mouse) ( 14 ) , DNAPK (mouse) ( 94 ) , ERK5 (human) ( 139 ) , FOXO1A (mouse) ( 108 ) , GPX1 (mouse) ( 134 ) , ICAM1 (mouse) ( 137 ) , ILK (mouse) ( 98 , 145 ) , ITGB1 (mouse) ( 89 ) , JNK1 (mouse) ( 52 ) , K17 (mouse) ( 116 ) , LIMS1 (human) ( 64 ) , LIMS1 (mouse) ( 64 ) , LIN28A (mouse) ( 46 ) , MCF2 (human) ( 107 ) , MEK5 (human) ( 139 ) , mTOR (mouse) ( 44 ) , Musashi-1 (mouse) ( 13 ) , NFkB-p100 (mouse) ( 6 ) , p70S6K (mouse) ( 44 ) , PDHK4 (mouse) ( 34 ) , PDK1 (human) ( 166 ) , PDK1 (mouse) ( 8 , 96 , 97 , 138 ) , PGGT1B (mouse) ( 7 ) , PHB (human) ( 82 ) , PIK3CA (mouse) ( 39 ) , PIK3R1 (mouse) ( 60 ) , PKCI (mouse) ( 152 ) , PKCT (mouse) ( 92 ) , PPP2CA (mouse) ( 87 ) , PPP2CB (mouse) ( 87 ) , PPP2R5B (mouse) ( 87 ) , PREX2 (mouse) ( 31 ) , PTEN (mouse) ( 10 , 19 , 21 , 91 , 115 ) , RAC1 (human) ( 107 ) , RAP1B (mouse) ( 11 ) , Raptor (mouse) ( 44 ) , RHEB (mouse) ( 44 , 105 ) , RHOA (human) ( 107 , 167 ) , RICTOR (human) ( 72 , 83 ) , RICTOR (mouse) ( 72 ) , ROCK1 (mouse) ( 85 ) , SCD (mouse) ( 129 ) , SH3BP2 (mouse) ( 106 ) , SHP-2 (mouse) ( 155 ) , SIGLEC7 (mouse) ( 26 ) , Sin1 (mouse) ( 90 , 112 ) , SMO (mouse) ( 4 ) , TCL1A (mouse) ( 169 ) , TMEM55B (mouse) ( 86 ) , TSC1 (mouse) ( 50 ) , TSC2 (mouse) ( 105 , 113 , 138 ) , TTC3 (human) ( 80 )
Putative in vivo kinases:
ERK1 (mouse) ( 151 ) , P38A (mouse) ( 136 ) , PDK1 (mouse) ( 79 , 92 )
Kinases, in vitro:
PDK1 (human) ( 160 , 170 ) , PDK1 (mouse) ( 146 )
Putative upstream phosphatases:
PTEN (mouse) ( 163 )
Phosphatases, in vitro:
PPP2CA (mouse) ( 166 )
Treatments:
acadesine ( 93 ) , activin ( 150 ) , adiponectin ( 16 , 105 ) , Akt_inhibitor_VIII ( 29 ) , alpha-mangostin ( 58 ) , AM251 ( 51 ) , amino_acids ( 65 ) , anti-CD28 ( 81 ) , anti-CD3 ( 3 , 60 , 61 ) , anti-CD3/CD28 ( 14 ) , anti-IgB ( 99 ) , anti-IgM ( 69 ) , anti-ITGAL ( 81 ) , apomorphine ( 126 ) , AS252424 ( 57 ) , atorvastatin ( 102 ) , axatomy ( 22 ) , BAPTA-AM ( 140 , 158 ) , BDNF ( 10 ) , butaprost ( 57 ) , BX795 ( 90 ) , calphostin_C ( 40 ) , calyculin_A ( 166 ) , cangrelor ( 140 ) , catalase ( 159 ) , cholera_toxin ( 135 ) , cocaine ( 151 ) , colforsin ( 127 , 165 ) , culturing_of_cells ( 37 ) , dactolisib ( 30 ) , doconexent ( 154 ) , EGF ( 10 , 31 , 48 , 62 , 86 , 112 , 135 , 155 , 165 ) , Epo ( 123 ) , estradiol ( 120 , 125 ) , exercise ( 98 ) , fasting ( 77 ) , FGF1 ( 95 , 153 ) , FGF2 ( 95 , 112 ) , fibrinogen ( 26 ) , fostriecin ( 126 ) , GDNF ( 96 ) , GF109203X ( 140 ) , glucose ( 52 ) , GM-CSF ( 84 , 101 ) , Go_6976 ( 61 ) , H2O2 ( 159 ) , haloperidol ( 141 ) , high-fat diet ( 34 ) , HU-210 ( 51 ) , hypoxia ( 52 ) , hypoxia/reoxygenation ( 52 ) , IBMX ( 127 ) , IC87114 ( 57 ) , IgE ( 130 ) , IGF-1 ( 24 , 31 , 115 , 118 , 119 , 138 , 161 , 170 ) , IL-22 ( 70 ) , IL-6 ( 70 , 150 ) , inflammation ( 70 ) , insulin ( 10 , 20 , 23 , 31 , 34 , 40 , 46 , 50 , 51 , 52 , 55 , 65 , 66 , 67 , 71 , 75 , 76 , 82 , 83 , 85 , 87 , 89 , 90 , 91 , 92 , 97 , 100 , 103 , 104 , 105 , 107 , 109 , 112 , 128 , 132 , 134 , 135 , 138 , 143 , 146 , 156 , 157 , 158 , 160 , 163 , 164 , 166 , 168 ) , ionizing_radiation ( 94 ) , ipatasertib ( 22 ) , ischemia ( 52 ) , KN-62 ( 66 ) , KU-0063794 ( 12 , 40 ) , L803-mts ( 121 ) , laminar flow ( 139 ) , levamfetamine ( 126 ) , LIF ( 131 ) , linoleic_acid ( 132 ) , long-term_potentiation ( 73 ) , low_cell_density ( 17 ) , LPA ( 157 ) , LPS ( 7 ) , lupeol ( 133 ) , LY294002 ( 40 , 60 , 109 , 115 , 123 , 126 , 136 , 140 , 153 , 157 , 164 , 167 , 168 ) , M-CSF ( 106 ) , meal feeding ( 50 ) , mechanical stress ( 29 , 40 ) , memantine ( 117 ) , miR-143 ( 55 ) , miRNA ( 14 ) , MK-2206 ( 22 ) , muscle contraction ( 66 , 110 ) , NAC ( 159 ) , neurotensin ( 135 ) , okadaic_acid ( 126 , 161 ) , palmitate ( 65 , 92 ) , PAR1-activating_peptide ( 140 ) , PAR4-activating_peptide ( 140 ) , PD98059 ( 153 , 164 , 168 ) , PDGF ( 31 , 75 , 92 , 112 , 170 ) , PGE2 ( 57 , 63 ) , phorbol_ester ( 118 , 122 , 133 , 140 ) , physostigmine ( 117 ) , PIK90 ( 90 ) , pilocarpine ( 117 ) , piroxicam ( 60 ) , PP242 ( 90 ) , progesterone ( 125 ) , PTX ( 57 , 135 ) , PUGNAc ( 71 , 156 ) , QL9_peptide ( 81 ) , quinpirole ( 151 ) , rapamycin ( 12 , 24 , 46 , 50 , 57 , 65 , 72 , 90 , 100 , 105 , 109 , 119 , 128 , 138 ) , refeeding ( 77 ) , SB202190 ( 164 ) , SB203580 ( 136 ) , serum ( 29 , 46 , 72 , 107 , 112 ) , serum_starvation ( 10 , 31 , 46 , 112 ) , serum_withdrawal ( 136 ) , siRNA ( 87 , 96 ) , SKF38393 ( 151 ) , skin aging ( 5 ) , SP600125 ( 52 ) , sphingomyelinase ( 9 ) , sphingosine_1-phosphate ( 21 ) , SR48527 ( 135 ) , SR49711 ( 135 ) , staurosporine ( 154 ) , sulprostone ( 57 ) , TGF-beta ( 14 , 150 , 167 ) , Theophylline ( 102 ) , thrombin ( 140 ) , TNF ( 113 , 161 ) , Torin1 ( 57 ) , triciribine ( 70 ) , troglitazone ( 114 , 119 ) , U0126 ( 6 , 96 , 102 , 127 , 151 , 153 ) , UV ( 152 , 159 , 164 ) , UVB ( 5 ) , vanadate ( 150 ) , wortmannin ( 10 , 23 , 57 , 65 , 71 , 76 , 107 , 119 , 151 , 157 , 169 ) , Y27632 ( 11 )

Downstream Regulation
Effects of modification on Akt1:
activity, induced ( 161 ) , enzymatic activity, induced ( 37 , 44 , 140 , 162 , 170 ) , molecular association, regulation ( 41 ) , protein degradation ( 41 ) , ubiquitination ( 41 )
Effects of modification on biological processes:
apoptosis, altered ( 37 , 162 ) , apoptosis, inhibited ( 86 ) , cell differentiation, induced ( 44 ) , cell growth, altered ( 70 , 86 ) , cytoskeletal reorganization ( 86 ) , neural plasticity ( 37 ) , RNA splicing, induced ( 3 ) , signaling pathway regulation ( 31 , 37 , 44 )
Induce interaction with:
CHIP (human) ( 41 )

Disease / Diagnostics Relevance
Relevant diseases:
colonic inflamation ( 60 )

References 

1

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2

Kamiyama M, et al. (2017) ASK1 facilitates tumor metastasis through phosphorylation of an ADP receptor P2Y12 in platelets. Cell Death Differ 24, 2066-2076
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3

Hawse WF, Boggess WC, Morel PA (2017) TCR Signal Strength Regulates Akt Substrate Specificity To Induce Alternate Murine Th and T Regulatory Cell Differentiation Programs. J Immunol 199, 589-597
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4

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5

Choi YJ, et al. (2016) The underlying mechanism of proinflammatory NF-κB activation by the mTORC2/Akt/IKKα pathway during skin aging. Oncotarget 7, 52685-52694
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6

Wang Y, et al. (2016) Tumor-suppressor NFκB2 p100 interacts with ERK2 and stabilizes PTEN mRNA via inhibition of miR-494. Oncogene 35, 4080-90
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7

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8

Du J, et al. (2016) PDK1 promotes tumor growth and metastasis in a spontaneous breast cancer model. Oncogene 35, 3314-23
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9

Apostolidis SA, et al. (2016) Phosphatase PP2A is requisite for the function of regulatory T cells. Nat Immunol 17, 556-64
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10

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11

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12

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13

Li N, et al. (2015) The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins. Cell Rep 13, 2440-55
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14

Singh Y, Garden OA, Lang F, Cobb BS (2015) MicroRNA-15b/16 Enhances the Induction of Regulatory T Cells by Regulating the Expression of Rictor and mTOR. J Immunol 195, 5667-77
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15

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16

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17

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18

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19

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20

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21

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22

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23

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24

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25

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26

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27

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28

Ryu J, et al. (2014) APPL1 Potentiates Insulin Sensitivity by Facilitating the Binding of IRS1/2 to the Insulin Receptor. Cell Rep 7, 1227-38
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29

Batra N, et al. (2014) Direct regulation of osteocytic connexin 43 hemichannels through AKT kinase activated by mechanical stimulation. J Biol Chem 289, 10582-91
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30

Lin A, et al. (2014) FoxO transcription factors promote AKT Ser473 phosphorylation and renal tumor growth in response to pharmacologic inhibition of the PI3K-AKT pathway. Cancer Res 74, 1682-93
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31

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33

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34

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35

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36

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37

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38

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40

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41

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42

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43

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44

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45

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46

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47

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48

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49

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50

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51

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52

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53

Xie X, et al. (2011) IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation. Proc Natl Acad Sci U S A 108, 6474-9
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54

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55

Jordan SD, et al. (2011) Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism. Nat Cell Biol 13, 434-46
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56

Rodgers JT, Vogel RO, Puigserver P (2011) Clk2 and B56β Mediate Insulin-Regulated Assembly of the PP2A Phosphatase Holoenzyme Complex on Akt. Mol Cell 41, 471-9
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57

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58

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59

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60

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