Tyr701

Site Information
DDPKRTGyIkTELIs SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 447754
Associated spectra: 1 CST

In vivo Characterization
Methods used to characterize site in vivo:	electrophoretic mobility shift ( 47 ) , flow cytometry ( 2 , 13 , 18 , 19 ) , immunoassay ( 6 ) , immunoprecipitation ( 1 ) , mass spectrometry ( 3 , 24 , 25 , 28 , 30 ) , mutation of modification site ( 1 , 14 , 15 , 18 , 20 , 21 , 31 , 49 ) , phospho-antibody ( 1 , 2 , 4 , 5 , 6 , 7 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 19 , 20 , 21 , 22 , 26 , 27 , 29 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 45 , 46 , 47 , 48 , 49 ) , western blotting ( 1 , 4 , 5 , 6 , 7 , 9 , 10 , 11 , 12 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 26 , 31 , 33 , 34 , 35 , 39 , 41 , 42 , 43 , 45 , 49 )
Disease tissue studied:	leukemia ( 35 ) , chronic myelogenous leukemia ( 35 ) , T cell leukemia ( 35 ) , liver cancer ( 5 , 14 ) , lymphoma ( 15 ) , Burkitt's lymphoma ( 15 ) , fibrosarcoma of soft tissue ( 15 , 21 )
Relevant cell line - cell type - tissue:	'brain, embryonic' ( 29 ) , 293 (epithelial) ( 1 , 14 , 38 ) , 3T3 (fibroblast) [STAT1 (mouse), homozygous knockout] ( 39 ) , 3T3 (fibroblast) ( 26 , 49 ) , aorta [ADORA2A (mouse), homozygous knockout] ( 10 ) , B lymphocyte-spleen ( 13 ) , BaF3 ('B lymphocyte, precursor') ( 7 , 17 , 19 , 24 , 25 , 28 , 30 ) , BMMC (mast) ( 6 ) , BV2 (microglia) ( 42 ) , C4HD (breast cell) ( 27 ) , cortical progenitor ( 29 ) , embryo ( 46 ) , endothelial-aorta ( 33 ) , fibroblast ( 40 ) , fibroblast-lung ( 26 ) , HEK293T (epithelial) ( 6 ) , HeLa (cervical) ( 1 ) , hematopoietic stem cells ( 2 ) , HepG2 (hepatic) ( 5 , 14 ) , J774 (macrophage) ( 20 ) , KT-1 (myeloid) ( 35 ) , L929 (fibroblast) ( 32 ) , LM (fibroblast) ( 11 ) , LM-TK (fibroblast) ( 11 ) , macrophage-bone marrow ( 4 , 5 , 36 ) , MEF (fibroblast) ( 5 , 6 , 12 , 14 , 15 , 31 , 34 , 43 , 45 ) , MEF (fibroblast) [IGF1R (mouse)] ( 38 ) , MEF (fibroblast) [Mnk1 (mouse), homozygous knockout] ( 9 ) , MEF (fibroblast) [Mnk2 (mouse), homozygous knockout] ( 9 ) , MEF (fibroblast) [P38A (mouse), homozygous knockout] ( 35 ) , MEF (fibroblast) [STAT1 (mouse), homozygous knockout] ( 18 ) , microglia ( 22 ) , MOLT-4 (T lymphocyte) ( 35 ) , neuron-'brain, cerebral cortex' ( 41 ) , neuron-'brain, cerebral cortex' [STAT1 (mouse), homozygous knockout] ( 41 ) , oocyte [CPEB (mouse)] ( 32 ) , RAMOS (B lymphocyte) ( 15 ) , RAW 264 (macrophage) ( 37 , 47 ) , RAW 264.7 (macrophage) ( 3 , 21 ) , SCC16-5 (fibroblast) ( 48 ) , splenocyte ( 19 ) , SYF (fibroblast) ( 31 ) , T lymphocyte-blood ( 16 ) , T lymphocyte-lymph node ( 13 ) , T lymphocyte-spleen ( 13 ) , T lymphocyte-thymus ( 45 ) , U3A (fibroblast) ( 15 , 21 )

Upstream Regulation
Regulatory protein:	ADORA2A (human) ( 10 ) , BCR-ABL1 (human) ( 17 ) , Mnk1 (mouse) ( 9 ) , Mnk2 (mouse) ( 9 ) , PKCD (mouse) ( 21 ) , SNX8 (mouse) ( 1 ) , SUMO1 (mouse) ( 6 )
Putative upstream phosphatases:	PTPN2 (human) ( 44 , 45 ) , SHP-2 (mouse) ( 40 )
Treatments:	AG490 ( 20 ) , anisomycin ( 14 ) , apigenin ( 20 ) , calyculin_A ( 38 ) , cardiotropin-1 ( 26 ) , DMSO ( 31 ) , flavopiridol ( 5 ) , G-CSF ( 7 ) , ganglioside ( 42 ) , guanosine ( 22 ) , H2O2 ( 15 ) , IFN-alpha ( 12 , 17 , 35 , 45 ) , IFN-beta ( 4 , 5 , 14 , 39 , 47 ) , IFN-gamma ( 1 , 2 , 5 , 6 , 9 , 13 , 14 , 16 , 20 , 21 , 22 , 31 , 32 , 33 , 37 , 38 , 40 , 43 , 45 , 48 , 49 ) , IL-11 ( 26 ) , IL-2 ( 19 ) , IL-21 ( 19 ) , IL-6 ( 26 ) , ischemia/reperfusion ( 41 ) , lactacystin ( 15 ) , LIF ( 26 , 29 ) , LPS ( 5 , 10 , 33 , 37 , 47 ) , LY294002 ( 20 , 37 ) , mifepristone ( 27 ) , MPA ( 27 ) , olomoucine ( 5 ) , oncostatin_M ( 26 ) , osmotic_stress ( 35 ) , rottlerin ( 21 , 37 ) , SB202190 ( 33 ) , SB203580 ( 15 , 37 ) , seliciclib ( 5 ) , staurosporine ( 6 , 45 ) , SU6656 ( 31 ) , TNF ( 11 ) , U0126 ( 15 ) , UV ( 43 ) , vitronectin ( 2 )

Downstream Regulation
Effects of modification on STAT1:	activity, inhibited ( 6 ) , intracellular localization ( 38 ) , molecular association, regulation ( 18 ) , phosphorylation ( 14 , 49 ) , sumoylation ( 6 )
Effects of modification on biological processes:	cell growth, altered ( 18 ) , transcription, induced ( 18 , 20 , 21 ) , transcription, inhibited ( 6 )
Induce interaction with:	DNA ( 18 )

Disease / Diagnostics Relevance
Relevant diseases:	lung cancer ( 18 )

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	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
3	Pinto SM, et al. (2015) Quantitative phosphoproteomic analysis of IL-33-mediated signaling. Proteomics 15, 532-44 25367039 Curated Info
4	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
5	Bancerek J, et al. (2013) CDK8 kinase phosphorylates transcription factor STAT1 to selectively regulate the interferon response. Immunity 38, 250-62 23352233 Curated Info
6	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
7	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
8	Bard-Chapeau EA, et al. (2011) Ptpn11/Shp2 acts as a tumor suppressor in hepatocellular carcinogenesis. Cancer Cell 19, 629-39 21575863 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	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
11	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
12	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
13	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
14	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
15	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
16	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
17	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
18	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
19	Zeng R, et al. (2007) The molecular basis of IL-21-mediated proliferation. Blood 109, 4135-42 17234735 Curated Info
20	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
21	Kwon MJ, et al. (2007) Role of PKCdelta in IFN-gamma-inducible CIITA gene expression. Mol Immunol 44, 2841-9 17346795 Curated Info
22	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
23	Song L, et al. (2006) Stat1 and SUMO modification. Blood 108, 3237-44 16857984 Curated Info
24	Goss V (2006) CST Curation Set: 1404; Year: 2006; Biosample/Treatment: cell line, BaF3/serum starved &'\|\|' IL3 starvation &'\|\|' Tpo; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
25	Goss V (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; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
26	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
27	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
28	Goss V (2005) CST Curation Set: 698; Year: 2005; Biosample/Treatment: cell line, BaF3/-; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
29	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
30	Goss V (2005) CST Curation Set: 670; Year: 2005; Biosample/Treatment: cell line, BaF3/serum starved &'\|\|' Tpo; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991 Curated Info
31	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
32	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
33	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
34	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
35	Li Y, et al. (2004) Role of p38alpha Map kinase in Type I interferon signaling. J Biol Chem 279, 970-9 14578350 Curated Info
36	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
37	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
38	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
39	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
40	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
41	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
42	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
43	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
44	Zhu W, Mustelin T, David M (2002) Arginine methylation of STAT1 regulates its dephosphorylation by T cell protein tyrosine phosphatase. J Biol Chem 277, 35787-90 12171910 Curated Info
45	ten Hoeve J, et al. (2002) Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol 22, 5662-8 12138178 Curated Info
46	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
47	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
48	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
49	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