Ser727
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Home > Phosphorylation Site Page: > Ser727  -  STAT1 (mouse)

Site Information
tDNLLPMsPEEFDEM   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447753

In vivo Characterization
Methods used to characterize site in vivo:
electrophoretic mobility shift ( 36 ) , flow cytometry ( 3 , 14 ) , immunoprecipitation ( 1 , 4 ) , mass spectrometry ( 2 , 4 , 5 , 7 , 10 ) , mutation of modification site ( 1 , 6 , 12 , 13 , 14 , 16 , 17 , 27 , 28 , 38 ) , phospho-antibody ( 1 , 3 , 4 , 6 , 8 , 9 , 11 , 12 , 13 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ) , western blotting ( 1 , 4 , 6 , 8 , 9 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 20 , 21 , 23 , 24 , 25 , 26 , 28 , 30 , 31 , 33 , 34 , 35 , 38 )
Disease tissue studied:
leukemia ( 26 ) , chronic myelogenous leukemia ( 26 ) , T cell leukemia ( 26 ) , liver cancer ( 6 , 12 ) , lymphoma ( 13 , 24 ) , anaplastic large cell lymphoma ( 24 ) , Burkitt's lymphoma ( 13 ) , fibrosarcoma of soft tissue ( 13 , 17 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 1 , 12 ) , 32Dcl3 (myeloid) [FLT3 (mouse), transfection, chimera with human FLT3-ITD mutant (corresponding to wild type P36888 ( 10 ) , 32Dcl3 (myeloid) ( 10 ) , 3T3 (fibroblast) [STAT1 (mouse), homozygous knockout] ( 31 ) , 3T3 (fibroblast) ( 38 ) , BaF3 ('B lymphocyte, precursor') [JAK3 (human), transfection] ( 2 ) , BMMC (mast) ( 8 ) , BV2 (microglia) ( 34 ) , C141 (epidermal) ( 24 ) , cortical progenitor ( 19 ) , endothelial-aorta ( 23 ) , fibroblast ( 32 ) , HeLa (cervical) ( 1 ) , hematopoietic stem cells ( 3 ) , HepG2 (hepatic) ( 6 , 12 ) , J774 (macrophage) ( 16 , 30 ) , JB (epithelial) ( 21 ) , JB-6 (lymphocyte) ( 24 ) , JB6 CI41 (epidermal) ( 28 ) , KT-1 (myeloid) ( 26 ) , L929 (fibroblast) ( 22 ) , macrophage-bone marrow ( 4 , 6 , 27 ) , macrophage-peritoneum ( 7 ) , MEF (fibroblast) ( 6 , 11 , 12 , 13 , 24 , 25 , 35 ) , MEF (fibroblast) [Mnk1 (mouse), homozygous knockout] ( 9 ) , MEF (fibroblast) [Mnk2 (mouse), homozygous knockout] ( 9 ) , MEF (fibroblast) [P38A (mouse), homozygous knockout] ( 26 ) , MEF (fibroblast) [STAT1 (mouse), homozygous knockout] ( 14 ) , microglia ( 18 ) , MOLT-4 (T lymphocyte) ( 26 ) , myocyte-heart ( 15 ) , neuron-'brain, cerebral cortex' ( 33 ) , neuron-'brain, cerebral cortex' [STAT1 (mouse), homozygous knockout] ( 33 ) , oocyte [CPEB (mouse)] ( 22 ) , osteoclast ( 20 ) , RAMOS (B lymphocyte) ( 13 ) , RAW 264 (macrophage) ( 29 , 36 ) , RAW 264.7 (macrophage) ( 17 ) , SCC16-5 (fibroblast) ( 37 ) , stromal ( 5 ) , U3A (fibroblast) ( 13 , 17 )

Upstream Regulation
Regulatory protein:
BTRC (mouse) ( 13 ) , CDK7 (mouse) ( 6 ) , CDK8 (mouse) ( 6 ) , CDK9 (mouse) ( 6 ) , eNOS (mouse) ( 15 ) , Mnk1 (mouse) ( 9 ) , Mnk2 (mouse) ( 9 ) , P38A (mouse) ( 28 ) , PKCD (mouse) ( 17 ) , SUMO1 (mouse) ( 8 )
Putative in vivo kinases:
CDK8 (human) ( 6 ) , ERK1 (human) ( 13 , 24 ) , ERK2 (mouse) ( 13 ) , JNK1 (mouse) ( 24 ) , P38A (mouse) ( 20 , 24 , 35 ) , P38B (human) ( 24 )
Kinases, in vitro:
CDK8 (mouse) ( 6 ) , ERK1 (human) ( 24 ) , ERK2 (mouse) ( 13 ) , JNK1 (human) ( 24 ) , P38A (human) ( 24 ) , P38B (human) ( 24 )
Putative upstream phosphatases:
SHP-2 (mouse) ( 32 )
Treatments:
actinomycin_D ( 6 ) , AG490 ( 16 , 30 ) , anisomycin ( 6 , 12 , 35 ) , apigenin ( 16 , 30 ) , DETA-NONOate ( 15 ) , EGCG ( 21 ) , EGF ( 28 , 38 ) , flavopiridol ( 6 ) , ganglioside ( 34 ) , guanosine ( 18 ) , H2O2 ( 13 ) , IFN-alpha ( 11 , 26 ) , IFN-beta ( 6 , 12 , 31 , 36 ) , IFN-gamma ( 3 , 6 , 8 , 9 , 12 , 16 , 17 , 18 , 22 , 23 , 27 , 29 , 30 , 31 , 32 , 35 , 37 , 38 ) , ischemia ( 5 ) , ischemia/reperfusion ( 15 , 33 ) , lactacystin ( 13 ) , LIF ( 19 ) , LPS ( 4 , 6 , 23 , 29 , 31 , 36 ) , LY294002 ( 16 , 21 , 29 ) , olomoucine ( 6 ) , osmotic_stress ( 26 ) , PD169316 ( 24 ) , PD98059 ( 21 , 24 , 30 , 38 ) , RANKL ( 20 ) , rottlerin ( 17 , 29 ) , SB202190 ( 21 , 23 , 24 ) , SB203580 ( 13 , 20 , 29 , 35 , 38 ) , seliciclib ( 6 ) , serum ( 38 ) , siRNA ( 6 ) , SP600125 ( 21 ) , staurosporine ( 8 ) , Theaflavins ( 21 ) , TNF ( 4 ) , U0126 ( 13 , 21 , 24 ) , UV ( 21 , 24 , 35 , 38 ) , vitronectin ( 3 ) , wortmannin ( 21 ) , Z-VAD-FMK ( 4 )

Downstream Regulation
Effects of modification on STAT1:
activity, induced ( 31 , 38 ) , activity, inhibited ( 8 ) , molecular association, regulation ( 13 ) , phosphorylation ( 6 ) , protein degradation ( 13 ) , sumoylation ( 8 )
Effects of modification on biological processes:
cell cycle regulation ( 14 ) , cell growth, altered ( 28 ) , signaling pathway regulation ( 6 ) , transcription, altered ( 6 , 38 ) , transcription, induced ( 16 , 17 , 27 , 31 ) , transcription, inhibited ( 8 )
Induce interaction with:
BTRC (mouse) ( 13 )

References 

1

Wei J, et al. (2017) SNX8 mediates IFNγ-triggered noncanonical signaling pathway and host defense against Listeria monocytogenes. Proc Natl Acad Sci U S A 114, 13000-13005
29180417   Curated Info

2

Degryse S, et al. (2017) Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia. Leukemia
28852199   Curated Info

3

Umemoto T, et al. (2017) Integrin αvβ3 enhances the suppressive effect of interferon-γ on hematopoietic stem cells. EMBO J 36, 2390-2403
28673932   Curated Info

4

Shutinoski B, et al. (2016) K45A mutation of RIPK1 results in poor necroptosis and cytokine signaling in macrophages, which impacts inflammatory responses in vivo. Cell Death Differ 23, 1628-37
27258786   Curated Info

5

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
24719451   Curated Info

6

Bancerek J, et al. (2013) CDK8 kinase phosphorylates transcription factor STAT1 to selectively regulate the interferon response. Immunity 38, 250-62
23352233   Curated Info

7

Wu X, et al. (2012) Investigation of receptor interacting protein (RIP3)-dependent protein phosphorylation by quantitative phosphoproteomics. Mol Cell Proteomics 11, 1640-51
22942356   Curated Info

8

Begitt A, Droescher M, Knobeloch KP, Vinkemeier U (2011) SUMO conjugation of STAT1 protects cells from hyperresponsiveness to IFNγ. Blood 118, 1002-7
21636857   Curated Info

9

Joshi S, et al. (2011) Essential role for Mnk kinases in type II interferon (IFNgamma) signaling and its suppressive effects on normal hematopoiesis. J Biol Chem 286, 6017-26
21149447   Curated Info

10

Choudhary C, et al. (2009) Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes. Mol Cell 36, 326-39
19854140   Curated Info

11

Joshi S, et al. (2009) Type I interferon (IFN)-dependent activation of Mnk1 and its role in the generation of growth inhibitory responses. Proc Natl Acad Sci U S A 106, 12097-102
19574459   Curated Info

12

Sadzak I, et al. (2008) Recruitment of Stat1 to chromatin is required for interferon-induced serine phosphorylation of Stat1 transactivation domain. Proc Natl Acad Sci U S A 105, 8944-9
18574148   Curated Info

13

Soond SM, et al. (2008) ERK and the F-box protein betaTRCP target STAT1 for degradation. J Biol Chem 283, 16077-83
18378670   Curated Info

14

Wang S, Raven JF, Durbin JE, Koromilas AE (2008) Stat1 phosphorylation determines Ras oncogenicity by regulating p27 kip1. PLoS One 3, e3476
18941537   Curated Info

15

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
17606840   Curated Info

16

Harvey EJ, Li N, Ramji DP (2007) Critical role for casein kinase 2 and phosphoinositide-3-kinase in the interferon-gamma-induced expression of monocyte chemoattractant protein-1 and other key genes implicated in atherosclerosis. Arterioscler Thromb Vasc Biol 27, 806-12
17255531   Curated Info

17

Kwon MJ, et al. (2007) Role of PKCdelta in IFN-gamma-inducible CIITA gene expression. Mol Immunol 44, 2841-9
17346795   Curated Info

18

D'Alimonte I, et al. (2007) Guanosine inhibits CD40 receptor expression and function induced by cytokines and beta amyloid in mouse microglia cells. J Immunol 178, 720-31
17202332   Curated Info

19

He F, et al. (2005) A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis. Nat Neurosci 8, 616-25
15852015   Curated Info

20

Kwak HB, et al. (2005) Monokine induced by interferon-gamma is induced by receptor activator of nuclear factor kappa B ligand and is involved in osteoclast adhesion and migration. Blood 105, 2963-9
15585657   Curated Info

21

Zykova TA, et al. (2005) The signal transduction networks required for phosphorylation of STAT1 at Ser727 in mouse epidermal JB6 cells in the UVB response and inhibitory mechanisms of tea polyphenols. Carcinogenesis 26, 331-42
15550455   Curated Info

22

Truchet S, et al. (2004) Presence of permanently activated signal transducers and activators of transcription in nuclear interchromatin granules of unstimulated mouse oocytes and preimplantation embryos. Biol Reprod 71, 1330-9
15189833   Curated Info

23

Huang H, Rose JL, Hoyt DG (2004) p38 Mitogen-activated protein kinase mediates synergistic induction of inducible nitric-oxide synthase by lipopolysaccharide and interferon-gamma through signal transducer and activator of transcription 1 Ser727 phosphorylation in murine aortic endothelial cells. Mol Pharmacol 66, 302-11
15266021   Curated Info

24

Zhang Y, et al. (2004) Evidence of STAT1 phosphorylation modulated by MAPKs, MEK1 and MSK1. Carcinogenesis 25, 1165-75
14963018   Curated Info

25

El-Hashemite N, et al. (2004) Perturbed IFN-gamma-Jak-signal transducers and activators of transcription signaling in tuberous sclerosis mouse models: synergistic effects of rapamycin-IFN-gamma treatment. Cancer Res 64, 3436-43
15150095   Curated Info

26

Li Y, et al. (2004) Role of p38alpha Map kinase in Type I interferon signaling. J Biol Chem 279, 970-9
14578350   Curated Info

27

Varinou L, et al. (2003) Phosphorylation of the Stat1 transactivation domain is required for full-fledged IFN-gamma-dependent innate immunity. Immunity 19, 793-802
14670297   Curated Info

28

He Z, et al. (2003) p38 Mitogen-activated protein kinase regulation of JB6 Cl41 cell transformation promoted by epidermal growth factor. J Biol Chem 278, 26435-42
12748197   Curated Info

29

Rhee SH, et al. (2003) Toll-like receptors 2 and 4 activate STAT1 serine phosphorylation by distinct mechanisms in macrophages. J Biol Chem 278, 22506-12
12686553   Curated Info

30

Blanchette J, Jaramillo M, Olivier M (2003) Signalling events involved in interferon-gamma-inducible macrophage nitric oxide generation. Immunology 108, 513-22
12667213   Curated Info

31

Pilz A, et al. (2003) Phosphorylation of the Stat1 transactivating domain is required for the response to type I interferons. EMBO Rep 4, 368-73
12671680   Curated Info

32

Wu TR, et al. (2002) SHP-2 is a dual-specificity phosphatase involved in Stat1 dephosphorylation at both tyrosine and serine residues in nuclei. J Biol Chem 277, 47572-80
12270932   Curated Info

33

Takagi Y, Harada J, Chiarugi A, Moskowitz MA (2002) STAT1 is activated in neurons after ischemia and contributes to ischemic brain injury. J Cereb Blood Flow Metab 22, 1311-8
12439288   Curated Info

34

Kim OS, Park EJ, Joe EH, Jou I (2002) JAK-STAT signaling mediates gangliosides-induced inflammatory responses in brain microglial cells. J Biol Chem 277, 40594-601
12191995   Curated Info

35

Ramsauer K, et al. (2002) p38 MAPK enhances STAT1-dependent transcription independently of Ser-727 phosphorylation. Proc Natl Acad Sci U S A 99, 12859-64
12232043   Curated Info

36

Jacobs AT, Ignarro LJ (2001) Lipopolysaccharide-induced expression of interferon-beta mediates the timing of inducible nitric-oxide synthase induction in RAW 264.7 macrophages. J Biol Chem 276, 47950-7
11602590   Curated Info

37

Nguyen H, Ramana CV, Bayes J, Stark GR (2001) Roles of phosphatidylinositol 3-kinase in interferon-gamma-dependent phosphorylation of STAT1 on serine 727 and activation of gene expression. J Biol Chem 276, 33361-8
11438544   Curated Info

38

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
11226159   Curated Info