Ser727
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Home > Phosphorylation Site Page: > Ser727  -  STAT3 (mouse)

Site Information
NtIDLPMsPRTLDSL   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 448191

In vivo Characterization
Methods used to characterize site in vivo:
flow cytometry ( 3 ) , immunoprecipitation ( 3 , 4 , 8 , 9 , 39 , 40 , 57 ) , mass spectrometry ( 1 , 8 , 10 , 11 , 13 , 14 , 16 , 17 , 19 , 20 , 21 , 22 , 24 , 25 , 27 , 30 , 31 , 33 ) , microscopy-colocalization with upstream kinase ( 53 ) , mutation of modification site ( 3 , 4 , 9 , 18 , 26 , 29 , 34 , 41 , 48 , 50 , 58 ) , phospho-antibody ( 2 , 3 , 4 , 5 , 7 , 8 , 9 , 12 , 18 , 26 , 28 , 29 , 32 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ) , western blotting ( 2 , 3 , 4 , 5 , 7 , 8 , 9 , 12 , 18 , 26 , 28 , 29 , 32 , 34 , 35 , 36 , 38 , 39 , 40 , 41 , 42 , 48 , 49 , 54 , 57 , 58 )
Disease tissue studied:
anthrax infection ( 25 ) , adrenal cancer ( 26 ) , pheochromocytoma ( 26 ) , bladder cancer ( 39 ) , leukemia ( 42 ) , liver cancer ( 18 , 29 ) , prostate cancer ( 34 ) , melanoma skin cancer ( 2 , 31 ) , colonic inflamation ( 10 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 11 , 17 ) , 'stem, embryonic' ( 32 ) , 32Dcl3 (myeloid) [FLT3 (mouse), transfection, chimera with human FLT3-ITD mutant (corresponding to wild type P36888 ( 30 ) , 3T3 (fibroblast) ( 40 , 58 ) , astrocyte [NF1 (mouse), homozygous knockout] ( 28 ) , B16 (melanocyte) ( 2 ) , BaF3 ('B lymphocyte, precursor') [JAK3 (human), transfection] ( 1 ) , BaF3 ('B lymphocyte, precursor') ( 55 ) , brain ( 53 ) , BV2 (microglia) ( 5 ) , C2C12 (myoblast) ( 48 ) , cortical progenitor ( 43 ) , COS (fibroblast) ( 34 , 51 , 57 ) , dendritic cell ( 3 ) , heart ( 27 ) , HEK293T (epithelial) ( 8 , 10 ) , hematopoietic progenitor ( 9 ) , hepatocyte ( 29 ) , HepG2 (hepatic) ( 18 , 29 , 45 ) , HL-1 (myocyte) [Akt1 (mouse), knockdown, stable lentiviral expression of Akt1 shRNA] ( 14 ) , HL-1 (myocyte) [Akt2 (mouse), knockdown, stable lentiviral expression of Akt2 shRNA] ( 14 ) , HL-1 (myocyte) ( 14 ) , J774 (macrophage) ( 54 ) , JB (epithelial) ( 56 ) , keratinocyte ( 41 ) , kidney ( 27 ) , L929 (fibroblast) ( 47 ) , liver ( 16 , 20 , 27 ) , lung ( 27 ) , lymph node ( 10 ) , macrophage-bone marrow ( 4 , 18 ) , macrophage-peritoneum ( 19 ) , mast-bone marrow ( 42 ) , MEF (fibroblast) ( 8 , 18 , 22 , 34 , 49 ) , MEF (fibroblast) [IGF1R (mouse)] ( 44 , 50 ) , MEF (fibroblast) [PIN1 (mouse)] ( 34 ) , MEF (fibroblast) [TSC2 (mouse), homozygous knockout] ( 22 ) , muscle ( 48 ) , myocyte-heart ( 35 , 37 ) , neuron-'brain, cerebral cortex' ( 26 ) , oocyte [CPEB (mouse)] ( 47 ) , PAM 212 (keratinocyte) ( 52 ) , pancreas ( 27 ) , PC-12 (chromaffin) [TrkA (rat), transfection] ( 21 ) , PC-12 (chromaffin) ( 21 , 26 ) , PC3 (prostate cell) ( 34 ) , preadipocyte ( 33 ) , preosteoclast ( 38 ) , RAW 264.7 (macrophage) ( 13 ) , RBL-2H3 (basophil) ( 42 ) , retinal ganglion ( 7 ) , skin ( 36 ) , skin [mGluR1 (mouse), transgenic, TG mutant mice] ( 31 ) , skin [PKCE (mouse)] ( 36 ) , spleen ( 25 , 27 ) , splenocyte ( 46 ) , T lymphocyte ( 10 ) , T lymphocyte-spleen ( 24 ) , T24 (bladder cell) ( 39 ) , testis ( 27 )

Upstream Regulation
Regulatory protein:
AT1 (mouse) ( 37 ) , eNOS (mouse) ( 35 ) , MEK1 (mouse) ( 7 ) , NF1 (mouse) ( 28 ) , PD-L1 (mouse) ( 2 ) , PKCD (mouse) ( 41 ) , PKCE (mouse) ( 36 )
Putative in vivo kinases:
CDK5 (mouse) ( 48 ) , CDK8 (human) ( 18 ) , IRAK1 (mouse) ( 46 ) , MEKK1 (mouse) ( 57 ) , MSK1 (mouse) ( 56 ) , mTOR (mouse) ( 9 ) , NLK (human) ( 45 ) , P38A (mouse) ( 49 ) , PKCD (mouse) ( 41 ) , PKCE (mouse) ( 36 ) , TBK1 (mouse) ( 3 )
Kinases, in vitro:
CDK5 (mouse) ( 48 ) , JNK1 (mouse) ( 56 ) , MEKK1 (mouse) ( 57 ) , MSK1 (mouse) ( 56 ) , NLK (human) ( 45 ) , PKCE (mouse) ( 36 )
Putative upstream phosphatases:
DUSP2 (human) ( 10 )
Treatments:
AG1478 ( 56 ) , amino_acids ( 29 ) , bradykinin ( 12 ) , CNTF ( 7 ) , CoCL2 ( 5 ) , cucurbitacin-I ( 28 ) , DETA-NONOate ( 35 ) , DNP ( 42 ) , EGF ( 12 , 39 , 51 , 57 , 58 ) , ethanol ( 53 ) , flavopiridol ( 18 ) , G-CSF ( 45 ) , Go_6983 ( 26 ) , GSK2334470 ( 11 ) , GSK650394 ( 11 ) , H-7 ( 45 , 54 ) , H-89 ( 56 ) , heparin sodium ( 38 ) , IFN-beta ( 2 , 18 ) , IFN-gamma ( 47 , 58 ) , IgE ( 42 ) , IL-10 ( 18 ) , IL-11 ( 38 ) , IL-6 ( 26 , 44 , 45 ) , insulin ( 9 , 11 , 17 , 41 ) , ischemia/reperfusion ( 35 ) , leptin ( 52 , 54 ) , LIF ( 32 , 43 ) , LPS ( 18 , 46 ) , LY294002 ( 11 , 49 , 56 ) , neuregulin ( 48 ) , NGF ( 26 ) , oncostatin_M ( 34 ) , PD153035 ( 56 ) , PD98059 ( 38 , 49 , 54 , 56 , 58 ) , PDGF ( 21 , 57 ) , propofol ( 5 ) , rapamycin ( 9 , 29 , 54 , 56 ) , refametinib ( 7 ) , rottlerin ( 41 ) , SB202190 ( 56 ) , SB203580 ( 26 , 58 ) , seliciclib ( 48 ) , serum ( 49 , 58 ) , siRNA ( 18 ) , SP600125 ( 26 , 38 ) , SU6656 ( 26 ) , TGF-beta ( 45 ) , Torin1 ( 11 ) , U0126 ( 7 , 26 ) , UV ( 36 , 56 , 58 ) , Y27632 ( 44 )

Downstream Regulation
Effects of modification on STAT3:
activity, induced ( 34 , 40 , 48 , 54 ) , intracellular localization ( 7 , 41 , 44 , 52 ) , molecular association, regulation ( 26 , 34 , 39 , 40 , 48 ) , phosphorylation ( 41 )
Effects of modification on biological processes:
cell differentiation, induced ( 10 ) , cell growth, altered ( 40 , 44 ) , cell growth, induced ( 26 ) , transcription, altered ( 39 ) , transcription, induced ( 3 , 9 , 12 , 34 , 48 , 50 , 52 , 57 )
Induce interaction with:
ANXA1 (mouse) ( 48 ) , DNA ( 39 , 54 ) , GRIM-19 (mouse) ( 26 ) , PDGFRA (mouse) ( 40 ) , PIN1 (mouse) ( 34 )
Inhibit interaction with:
DNA ( 48 )

References 

1

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2

Gato-Cañas M, et al. (2017) PDL1 Signals through Conserved Sequence Motifs to Overcome Interferon-Mediated Cytotoxicity. Cell Rep 20, 1818-1829
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3

Xiao Y, et al. (2017) The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity. J Exp Med 214, 1493-1507
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4

Li X, et al. (2017) Myeloid-derived cullin 3 promotes STAT3 phosphorylation by inhibiting OGT expression and protects against intestinal inflammation. J Exp Med 214, 1093-1109
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5

Lu Y, et al. (2017) Intracellular Ca2+ homeostasis and JAK1/STAT3 pathway are involved in the protective effect of propofol on BV2 microglia against hypoxia-induced inflammation and apoptosis. PLoS One 12, e0178098
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6

Sacco F, et al. (2016) Glucose-regulated and drug-perturbed phosphoproteome reveals molecular mechanisms controlling insulin secretion. Nat Commun 7, 13250
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7

Luo X, et al. (2016) Enhanced Transcriptional Activity and Mitochondrial Localization of STAT3 Co-induce Axon Regrowth in the Adult Central Nervous System. Cell Rep 15, 398-410
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8

Ulaganathan VK, Sperl B, Rapp UR, Ullrich A (2015) Germline variant FGFR4  p.G388R exposes a membrane-proximal STAT3 binding site. Nature 528, 570-4
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9

Xia P, et al. (2015) Insulin-InsR signaling drives multipotent progenitor differentiation toward lymphoid lineages. J Exp Med 212, 2305-21
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10

Lu D, et al. (2015) The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates TH17 differentiation. Nat Immunol 16, 1263-73
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11

Parker BL, et al. (2015) Targeted phosphoproteomics of insulin signaling using data-independent acquisition mass spectrometry. Sci Signal 8, rs6
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12

Breit A, et al. (2015) Serine-727 Phosphorylation Activates Hypothalamic STAT-3 Independently From Tyrosine-705 Phosphorylation. Mol Endocrinol 29, 445-59
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13

Pinto SM, et al. (2015) Quantitative phosphoproteomic analysis of IL-33-mediated signaling. Proteomics 15, 532-44
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14

Reinartz M, Raupach A, Kaisers W, Gödecke A (2014) AKT1 and AKT2 induce distinct phosphorylation patterns in HL-1 cardiac myocytes. J Proteome Res 13, 4232-45
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15

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
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16

Wilson-Grady JT, Haas W, Gygi SP (2013) Quantitative comparison of the fasted and re-fed mouse liver phosphoproteomes using lower pH reductive dimethylation. Methods 61, 277-86
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17

Humphrey SJ, et al. (2013) Dynamic Adipocyte Phosphoproteome Reveals that Akt Directly Regulates mTORC2. Cell Metab 17, 1009-20
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18

Bancerek J, et al. (2013) CDK8 kinase phosphorylates transcription factor STAT1 to selectively regulate the interferon response. Immunity 38, 250-62
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19

Wu X, et al. (2012) Investigation of receptor interacting protein (RIP3)-dependent protein phosphorylation by quantitative phosphoproteomics. Mol Cell Proteomics 11, 1640-51
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20

Grimsrud PA, et al. (2012) A quantitative map of the liver mitochondrial phosphoproteome reveals posttranslational control of ketogenesis. Cell Metab 16, 672-83
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21

Biarc J, Chalkley RJ, Burlingame AL, Bradshaw RA (2012) The induction of serine/threonine protein phosphorylations by a PDGFR/TrkA chimera in stably transfected PC12 cells. Mol Cell Proteomics 11, 15-30
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22

Yu Y, et al. (2011) Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332, 1322-6
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23

Bard-Chapeau EA, et al. (2011) Ptpn11/Shp2 acts as a tumor suppressor in hepatocellular carcinogenesis. Cancer Cell 19, 629-39
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24

Navarro MN, et al. (2011) Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes. Nat Immunol 12, 352-61
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25

Manes NP, et al. (2011) Discovery of mouse spleen signaling responses to anthrax using label-free quantitative phosphoproteomics via mass spectrometry. Mol Cell Proteomics 10, M110.000927
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26

Zhou L, Too HP (2011) Mitochondrial localized STAT3 is involved in NGF induced neurite outgrowth. PLoS One 6, e21680
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27

Huttlin EL, et al. (2010) A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143, 1174-89
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28

Banerjee S, et al. (2010) The neurofibromatosis type 1 tumor suppressor controls cell growth by regulating signal transducer and activator of transcription-3 activity in vitro and in vivo. Cancer Res 70, 1356-66
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29

Kim JH, Yoon MS, Chen J (2009) Signal transducer and activator of transcription 3 (STAT3) mediates amino acid inhibition of insulin signaling through serine 727 phosphorylation. J Biol Chem 284, 35425-32
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30

Choudhary C, et al. (2009) Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes. Mol Cell 36, 326-39
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31

Zanivan S, et al. (2008) Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry. J Proteome Res 7, 5314-26
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32

Li P, et al. (2008) Germline competent embryonic stem cells derived from rat blastocysts. Cell 135, 1299-310
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33

Krüger M, et al. (2008) Dissection of the insulin signaling pathway via quantitative phosphoproteomics. Proc Natl Acad Sci U S A 105, 2451-6
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34

Lufei C, Koh TH, Uchida T, Cao X (2007) Pin1 is required for the Ser727 phosphorylation-dependent Stat3 activity. Oncogene 26, 7656-64
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35

Xuan YT, et al. (2007) Endothelial nitric oxide synthase plays an obligatory role in the late phase of ischemic preconditioning by activating the protein kinase C epsilon p44/42 mitogen-activated protein kinase pSer-signal transducers and activators of transcription1/3 pathway. Circulation 116, 535-44
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36

Aziz MH, Manoharan HT, Verma AK (2007) Protein kinase C epsilon, which sensitizes skin to sun's UV radiation-induced cutaneous damage and development of squamous cell carcinomas, associates with Stat3. Cancer Res 67, 1385-94
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37

Zhai P, et al. (2006) An angiotensin II type 1 receptor mutant lacking epidermal growth factor receptor transactivation does not induce angiotensin II-mediated cardiac hypertrophy. Circ Res 99, 528-36
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38

Rajgopal R, Butcher M, Weitz JI, Shaughnessy SG (2006) Heparin synergistically enhances interleukin-11 signaling through up-regulation of the MAPK pathway. J Biol Chem 281, 20780-7
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39

Itoh M, et al. (2006) Requirement of STAT3 activation for maximal collagenase-1 (MMP-1) induction by epidermal growth factor and malignant characteristics in T24 bladder cancer cells. Oncogene 25, 1195-204
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40

Kumar RN, Shore SK, Dhanasekaran N (2006) Neoplastic transformation by the gep oncogene, Galpha12, involves signaling by STAT3. Oncogene 25, 899-906
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41

Gartsbein M, et al. (2006) The role of protein kinase C delta activation and STAT3 Ser727 phosphorylation in insulin-induced keratinocyte proliferation. J Cell Sci 119, 470-81
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42

Sonnenblick A, Levy C, Razin E (2005) Immunological trigger of mast cells by monomeric IgE: effect on microphthalmia transcription factor, STAT3 network of interactions. J Immunol 175, 1450-5
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43

He F, et al. (2005) A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis. Nat Neurosci 8, 616-25
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44

Debidda M, et al. (2005) A role of STAT3 in Rho GTPase-regulated cell migration and proliferation. J Biol Chem 280, 17275-85
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45

Kojima H, et al. (2005) STAT3 regulates Nemo-like kinase by mediating its interaction with IL-6-stimulated TGFbeta-activated kinase 1 for STAT3 Ser-727 phosphorylation. Proc Natl Acad Sci U S A 102, 4524-9
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46

Huang Y, Li T, Sane DC, Li L (2004) IRAK1 serves as a novel regulator essential for lipopolysaccharide-induced interleukin-10 gene expression. J Biol Chem 279, 51697-703
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47

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48

Fu AK, et al. (2004) Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of transcription 3 and regulates its transcriptional activity. Proc Natl Acad Sci U S A 101, 6728-33
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49

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50

Shen Y, et al. (2004) Essential role of STAT3 in postnatal survival and growth revealed by mice lacking STAT3 serine 727 phosphorylation. Mol Cell Biol 24, 407-19
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51

Zhang T, Ma J, Cao X (2003) Grb2 regulates Stat3 activation negatively in epidermal growth factor signalling. Biochem J 376, 457-64
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52

Goren I, Pfeilschifter J, Frank S (2003) Determination of leptin signaling pathways in human and murine keratinocytes. Biochem Biophys Res Commun 303, 1080-5
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53

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54

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55

Zhang Q, et al. (2002) Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma. J Immunol 168, 466-74
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56

Zhang Y, Liu G, Dong Z (2001) MSK1 and JNKs mediate phosphorylation of STAT3 in UVA-irradiated mouse epidermal JB6 cells. J Biol Chem 276, 42534-42
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57

Lim CP, Cao X (2001) Regulation of Stat3 activation by MEK kinase 1. J Biol Chem 276, 21004-11
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58

Kovarik P, et al. (2001) Specificity of signaling by STAT1 depends on SH2 and C-terminal domains that regulate Ser727 phosphorylation, differentially affecting specific target gene expression. EMBO J 20, 91-100
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