Tyr701

Site Information
DDPKRTGyIkTELIS SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 447754

In vivo Characterization
Methods used to characterize site in vivo:	electrophoretic mobility shift ( 8 ) , mutation of modification site ( 14 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ) , western blotting ( 1 , 2 , 4 , 6 , 11 , 12 , 13 , 14 , 15 , 16 )
Disease tissue studied:	bone cancer ( 1 ) , liver cancer ( 12 )
Relevant cell line - cell type - tissue:	'brain, cerebral cortex' ( 11 ) , 'muscle, skeletal' ( 10 ) , 'neuron, cerebellar granule'-brain ( 9 ) , 'neuron, hippocampal, CA1 pyramidal'-brain ( 2 ) , astrocyte-'brain, striatum' ( 6 ) , FRTL-5 (thyroid cell) ( 13 , 16 ) , granulosa ( 15 ) , H4IIe (hepatic) ( 12 ) , heart ( 4 ) , hepatocyte-liver ( 8 ) , HIT-T15 (pancreatic) ( 7 ) , liver ( 10 ) , myocyte-heart ( 5 , 14 ) , RAEC (endothelial) ( 3 ) , RIN (epithelial) ( 7 ) , U3A (fibroblast) ( 14 ) , UMR106 (bone cell) ( 1 )

Upstream Regulation
Regulatory protein:	LEPR (mouse) ( 7 ) , PIAS1 (human) ( 2 ) , SOCS1 (mouse) ( 16 ) , SOCS3 (mouse) ( 16 )
Treatments:	AG490 ( 6 , 8 , 11 ) , colforsin ( 16 ) , fludarabine ( 8 ) , G-CSF ( 5 ) , ganglioside ( 11 ) , GH ( 1 , 7 , 10 ) , H2O2 ( 6 , 13 ) , hypoxia/reoxygenation ( 8 ) , IFN-gamma ( 4 , 6 , 13 , 16 ) , IL-10 ( 6 ) , IL-22 ( 12 ) , IL-6 ( 6 , 7 ) , ischemia/reperfusion ( 4 , 9 ) , leptin ( 7 ) , methimazole ( 13 ) , NAC ( 8 ) , oxysterol ( 3 ) , pregnancy ( 15 ) , PRL ( 15 ) , rottlerin ( 15 ) , sepsis ( 10 ) , simvastatin ( 1 ) , tempol ( 4 ) , TSH ( 16 )

Upstream Regulation

Regulatory protein:

LEPR (mouse) ( 7 ) , PIAS1 (human) ( 2 ) , SOCS1 (mouse) ( 16 ) , SOCS3 (mouse) ( 16 )

Treatments:

AG490 ( 6 , 8 , 11 ) , colforsin ( 16 ) , fludarabine ( 8 ) , G-CSF ( 5 ) , ganglioside ( 11 ) , GH ( 1 , 7 , 10 ) , H2O2 ( 6 , 13 ) , hypoxia/reoxygenation ( 8 ) , IFN-gamma ( 4 , 6 , 13 , 16 ) , IL-10 ( 6 ) , IL-22 ( 12 ) , IL-6 ( 6 , 7 ) , ischemia/reperfusion ( 4 , 9 ) , leptin ( 7 ) , methimazole ( 13 ) , NAC ( 8 ) , oxysterol ( 3 ) , pregnancy ( 15 ) , PRL ( 15 ) , rottlerin ( 15 ) , sepsis ( 10 ) , simvastatin ( 1 ) , tempol ( 4 ) , TSH ( 16 )

Downstream Regulation
Effects of modification on STAT1:	activity, induced ( 8 ) , molecular association, regulation ( 2 )
Effects of modification on biological processes:	apoptosis, inhibited ( 8 ) , transcription, altered ( 8 , 14 )
Induce interaction with:	DNA ( 2 )

References
1	Sandoval-Usme MC, et al. (2014) Simvastatin impairs growth hormone-activated signal transducer and activator of transcription (STAT) signaling pathway in UMR-106 osteosarcoma cells. PLoS One 9, e87769 24489959 Curated Info
2	Tai DJ, et al. (2011) Novel role and mechanism of protein inhibitor of activated STAT1 in spatial learning. EMBO J 30, 205-20 21102409 Curated Info
3	Romeo GR, Kazlauskas A (2008) Oxysterol and diabetes activate STAT3 and control endothelial expression of profilin-1 via OSBP1. J Biol Chem 283, 9595-605 18230613 Curated Info
4	McCormick J, et al. (2006) Free radical scavenging inhibits STAT phosphorylation following in vivo ischemia/reperfusion injury. FASEB J 20, 2115-7 16935931 Curated Info
5	Harada M, et al. (2005) G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes. Nat Med 11, 305-11 15723072 Curated Info
6	Gorina R, Petegnief V, Chamorro A, Planas AM (2005) AG490 prevents cell death after exposure of rat astrocytes to hydrogen peroxide or proinflammatory cytokines: involvement of the Jak2/STAT pathway. J Neurochem 92, 505-18 15659221 Curated Info
7	Hekerman P, et al. (2005) Pleiotropy of leptin receptor signalling is defined by distinct roles of the intracellular tyrosines. FEBS J 272, 109-19 15634336 Curated Info
8	Terui K, et al. (2004) Hypoxia/re-oxygenation-induced, redox-dependent activation of STAT1 (signal transducer and activator of transcription 1) confers resistance to apoptotic cell death via hsp70 induction. Biochem J 380, 203-9 14984365 Curated Info
9	West DA, et al. (2004) MR image-guided investigation of regional signal transducers and activators of transcription-1 activation in a rat model of focal cerebral ischemia. Neuroscience 127, 333-9 15262323 Curated Info
10	Hong-Brown LQ, et al. (2003) Sepsis-induced muscle growth hormone resistance occurs independently of STAT5 phosphorylation. Am J Physiol Endocrinol Metab 285, E63-72 12644450 Curated Info
11	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
12	Lejeune D, et al. (2002) Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line. Pathways that are shared with and distinct from IL-10. J Biol Chem 277, 33676-82 12087100 Curated Info
13	Kim H, et al. (2001) Methimazole as an antioxidant and immunomodulator in thyroid cells: mechanisms involving interferon-gamma signaling and H(2)O(2) scavenging. Mol Pharmacol 60, 972-80 11641425 Curated Info
14	Stephanou A, et al. (2001) Induction of apoptosis and Fas receptor/Fas ligand expression by ischemia/reperfusion in cardiac myocytes requires serine 727 of the STAT-1 transcription factor but not tyrosine 701. J Biol Chem 276, 28340-7 11309387 Curated Info
15	Peters CA, et al. (2000) Induction of relaxin messenger RNA expression in response to prolactin receptor activation requires protein kinase C delta signaling. Mol Endocrinol 14, 576-90 10770494 Curated Info
16	Park ES, et al. (2000) Thyrotropin induces SOCS-1 (suppressor of cytokine signaling-1) and SOCS-3 in FRTL-5 thyroid cells. Mol Endocrinol 14, 440-8 10707961 Curated Info