Tyr701
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Phosphorylation Site Page:
Tyr701 - STAT1 (mouse)

Site Information
DDPKRTGyIKTELIS    SwissProt Entrez-Gene
Predicted information: Scansite
Orthologous residues: STAT1 (rat): Y701, STAT1 (human): Y701
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447754
Available spectra:  1 CST

In vivo Characterization
Methods used to characterize site in vivo: electrophoretic mobility shift (42), flow cytometry (10, 15, 16), mass spectrometry (20, 21, 24, 26), mutation of modification site (11, 12, 15, 17, 18, 27, 44), phospho-antibody (6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19, 22, 23, 25, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44), western blotting (6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 22, 27, 29, 30, 31, 35, 37, 38, 39, 40, 44)
Disease tissue studied: leukemia (31), chronic myelogenous leukemia (31), T cell leukemia (31), liver cancer (11), lymphoma (12), Burkitt's lymphoma (12), fibrosarcoma of soft tissue (12, 18)
Relevant cell line - cell type - tissue: 'brain, embryonic' (25), 293 (epithelial) (11, 34), 3T3 (fibroblast) (22, 44), 3T3 (fibroblast) [STAT1 (mouse), homozygous knockout] (35), aorta [ADORA2A (mouse), homozygous knockout] (7), B lymphocyte-spleen (10), BaF3 ('B lymphocyte, precursor') (14, 16, 20, 21, 24, 26), BV2 (microglia) (38), C4HD (breast cell) (23), cortical progenitor (25), embryo (41), endothelial-aorta (29), fibroblast (36), fibroblast-lung (22), HepG2 (hepatic) (11), J774 (macrophage) (17), KT-1 (myeloid) (31), L929 (fibroblast) (28), LM (fibroblast) (8), LM-TK (fibroblast) (8), macrophage-bone marrow (32), MEF (fibroblast) (9, 11, 12, 27, 30, 39, 40), MEF (fibroblast) [IGF1R (mouse)] (34), MEF (fibroblast) [Mnk1 (mouse), homozygous knockout] (6), MEF (fibroblast) [Mnk2 (mouse), homozygous knockout] (6), MEF (fibroblast) [P38A (mouse), homozygous knockout] (31), MEF (fibroblast) [STAT1 (mouse), homozygous knockout] (15), microglia (19), MOLT-4 (T lymphocyte) (31), neuron-'brain, cerebral cortex' (37), neuron-'brain, cerebral cortex' [STAT1 (mouse), homozygous knockout] (37), oocyte [CPEB (mouse)] (28), RAMOS (B lymphocyte) (12), RAW 264 (macrophage) (33, 42), RAW 264.7 (macrophage) (18), SCC16-5 (fibroblast) (43), splenocyte (16), SYF (fibroblast) (27), T lymphocyte-blood (13), T lymphocyte-lymph node (10), T lymphocyte-spleen (10), T lymphocyte-thymus (40), U3A (fibroblast) (12, 18)

Controlled by
Regulatory protein: ADORA2A (human) (7), Bcr/Abl (human) (14), Mnk1 (mouse) (6), Mnk2 (mouse) (6), PKCD (mouse) (18)
Putative upstream phosphatases: PTPN2 (human) (40), SHP-2 (mouse) (36)
Treatments: AG490 (17), anisomycin (11), apigenin (17), calyculin A (34), DMSO (27), ganglioside (38), H2O2 (12), IFN-alpha (9, 14, 31, 40), IFN-beta (11, 35, 42), IFN-gamma (6, 10, 11, 13, 17, 18, 19, 27, 28, 29, 33, 34, 36, 39, 40, 43, 44), IL-2 (16), IL-21 (16), IL-6 (22), ischemia/reperfusion (37), lactacystin (12), LIF (22, 25), LPS (7, 29, 33, 42), LY294002 (17, 33), MPA (23), oncostatin M (22), osmotic stress (31), rottlerin (18, 33), RU-486 (23), SB202190 (29), SB203580 (12, 33), staurosporine (40), SU6656 (27), TNF (8), U0126 (12), UV (39)

Downstream Regulation
Effects of modification on STAT1: intracellular localization (34), molecular association, regulation (15), phosphorylation (11, 44)
Effects of modification on biological processes: cell growth, altered (15), transcription, induced (15, 17, 18)
Induce interaction with: DNA (15)

Disease / Diagnostics Relevance
Relevant diseases: lung cancer (15)

References

1

Chiang HS, et al. (2014) GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses. Nat Immunol 15, 63-71
24270516   Curated Info

2

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

3

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

4

Futami M, et al. (2011) G-CSF receptor activation of the Src kinase Lyn is mediated by Gab2 recruitment of the Shp2 phosphatase. Blood 118, 1077-86
21636860   Curated Info

5

Bard-Chapeau EA, et al. (2011) Ptpn11/Shp2 acts as a tumor suppressor in hepatocellular carcinogenesis. Cancer Cell 19, 629-39
21575863   Curated Info

6

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

7

Safhi MM, et al. (2010) Priming of signal transducer and activator of transcription proteins for cytokine-triggered polyubiquitylation and degradation by the A 2A adenosine receptor. Mol Pharmacol 77, 968-78
20185553   Curated Info

8

Singh K, Sinha S, Malonia SK, Chattopadhyay S (2010) Tumor Necrosis Factor alpha (TNFalpha) regulates CD40 expression through SMAR1 phosphorylation. Biochem Biophys Res Commun 391, 1255-61
20006573   Curated Info

9

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

10

Hao Z, et al. (2008) Fas receptor expression in germinal-center B cells is essential for T and B lymphocyte homeostasis. Immunity 29, 615-27
18835195   Curated Info

11

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

12

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

13

Shi M, Lin TH, Appell KC, Berg LJ (2008) Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation. Immunity 28, 763-73
18549798   Curated Info

14

Katsoulidis E, et al. (2008) Suppression of interferon (IFN)-inducible genes and IFN-mediated functional responses in BCR-ABL-expressing cells. J Biol Chem 283, 10793-803
18287094   Curated Info

15

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

16

Zeng R, et al. (2007) The molecular basis of IL-21-mediated proliferation. Blood 109, 4135-42
17234735   Curated Info

17

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

18

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

19

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

20

(2006) CST Curation Set: 1404; Year: 2006; Biosample/Treatment: cell line, BaF3/serum starved & IL3 starvation & Tpo; Disease: chronic myelogenous leukemia; SILAC: -; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-pTyr Antibody Used to Purify Peptides prior to MS2: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991
Curated Info

21

(2006) CST Curation Set: 1406; Year: 2006; Biosample1/Treatment/Isotope: cell line, BaF3/serum starved & IL3 starvation & Tpo/L, Biosample2/Treatment/Isotope: cell line, BaF3/serum starved & IL3 starvation & Tpo/H; Disease: chronic myelogenous leukemia; SILAC: Y; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-pTyr Antibody Used to Purify Peptides prior to MS2: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991
Curated Info

22

Fritz DK, et al. (2006) Oncostatin-M up-regulates VCAM-1 and synergizes with IL-4 in eotaxin expression: involvement of STAT6. J Immunol 176, 4352-60
16547273   Curated Info

23

Proietti C, et al. (2005) Progestins induce transcriptional activation of signal transducer and activator of transcription 3 (Stat3) via a Jak- and Src-dependent mechanism in breast cancer cells. Mol Cell Biol 25, 4826-40
15923602   Curated Info

24

(2005) CST Curation Set: 698; Year: 2005; Biosample/Treatment: cell line, BaF3/-; Disease: chronic myelogenous leukemia; SILAC: -; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-pTyr Antibody Used to Purify Peptides prior to MS2: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991
Curated Info

25

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

26

(2005) CST Curation Set: 670; Year: 2005; Biosample/Treatment: cell line, BaF3/serum starved & Tpo; Disease: chronic myelogenous leukemia; SILAC: -; Specificity of Antibody Used to Purify Peptides prior to MS2: anti-pTyr Antibody Used to Purify Peptides prior to MS2: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991
Curated Info

27

Qing Y, Stark GR (2004) Alternative activation of STAT1 and STAT3 in response to interferon-gamma. J Biol Chem 279, 41679-85
15284232   Curated Info

28

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

29

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

30

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

31

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

32

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

33

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

34

Ivaska J, Bosca L, Parker PJ (2003) PKCepsilon is a permissive link in integrin-dependent IFN-gamma signalling that facilitates JAK phosphorylation of STAT1. Nat Cell Biol 5, 363-9
12640464   Curated Info

35

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

36

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

37

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

38

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

39

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

40

ten Hoeve J, et al. (2002) Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol 22, 5662-8
12138178   Curated Info

41

Bhunia AK, et al. (2002) PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell 109, 157-68
12007403   Curated Info

42

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

43

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

44

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

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