Regulatory circuits of the STAT3 signaling pathway (Homo sapiens)

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1Receptors with shared yc (IL2RG)-subunitplaceholdermiR-135a-5pmiR-17-5pmiR-29bmiR-124miR-519aType II receptorsNucleusReceptors with shared GP130 (IL6ST) subunitReceptor tyrosine kinasesHomodimeric cytokine receptorsReceptors with shared Bc (CSF2RB)-subunitG-protein coupled receptorsTranslocationPTPRTJAK2STAT3IL2RAPIAS3IL9RIFNAR2AKT1S1IL11RAF2RL3F2RIL6RMAPK12LIFRIL27RASTMN1MAPK11SETD7IL5RAMAPK3IL20RBCSF3RSRCAGTR1IL20RAIL6STIL3RAIFNLR1DUSP2MAPK10CSF2RBIL2RGMAPK1SOCS3IL10RAIL7RPRKCBPDGFRAMAPK8IL2RBMTORMAPK9IL10RBIL21RCNTFRIL12RB2AGTR2MAPK14IFNGR1CTF1MAPK13CREBBPMLST8PDGFRBMLST8MAPK15TRIM28EGFRIFNAR1MPLIL15RAMAPKAP1GHRIFNGR2RPTORMAPK6IL22RA1CSF2RAPTPRCF2RL2DEPTOROSMRPTPRDMAPK7RICTORPSTAT3PSTAT3STAT3MAPK4MTORIL6STIL6STIL6STIL6STIL6STIL6STIL6STIL2RGIL2RGIL2RBIL2RGIL2RGCSF2RBCSF2RBGHRMPLCSF3RIL10RBIL10RAIL10RBIL22RA1IL20RBIL10RBPDGFRAPDGFRBPDGFRBPDGFRAdephosphorylationphosphorilationdephosphorilationplaceholdermiR-19aplaceholdermiR-7aJAK1JAK2TYK2JAK1TYK2JAK1JAK3JAK2JAK2TYK2JAK1JAK2JAK2STAT3PSTAT3PSTAT3STAT3STAT3PTranslocationSTAT3STAT3PPPPSTAT3PSTAT3PSTAT3PPSTAT3PPSTAT3PMPSTAT3PMPSTAT3ASTAT3PPPAPmethylationacetylationSTAT3STAT3PMPMSTAT3APSTAT3APTranslocation


Description

STAT3 activation works through phosphorylation on at tyrosine 705 by a variety of adaptor kinases (JAK1, JAK2, JAK3, TYK2, SRC), resulting in dimers of STAT3 that translocates into the nucleus. Those adaptor kinases can be activated by a variety of receptors in response to cytokines or growth factors. Besides, an additional phosphate group can be added at serine 727 on each STAT3 (by MAPKs, mTOR, PKC), which enhances the transcriptional activity of STAT3 or directs STAT3 towards the mitochondria. Inside the nucleus, the STAT3 dimers are regulated by a variety of modifying factors, such as acetylation at lysine 685 by histone acetyltransferases, methylation at lysine 140 by histone methyltransferases to favor or impair STAT3 transcriptional activity, respectively. Other regulators of STAT3 include phosphatases (such as PTPRD, SOCS3, TRIM28, PIAS3) and miRNAs.

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Ontology Terms

 

Bibliography

  1. Roca Suarez AA, Van Renne N, Baumert TF, Lupberger J; ''Viral manipulation of STAT3: Evade, exploit, and injure.''; PLoS Pathog, 2018 PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
104390view13:38, 23 May 2019Marvin M2Modified description
104330view13:54, 17 May 2019FehrhartOntology Term : 'Jak-Stat signaling pathway' added !
104010view14:45, 25 April 2019Marvin M2Added all chemical conversions
103689view16:32, 28 March 2019Marvin M2Added binding information
103381view09:13, 25 February 2019DeSlAdded more details about dephosphorylation/phosphorylation modifications.
103379view09:03, 25 February 2019DeSlAdded some details as requested by Marvin
103333view12:24, 22 February 2019DeSlOntology Term : 'regulatory pathway' added !
103332view12:01, 22 February 2019Marvin M2Removed abundant nodes
103331view12:00, 22 February 2019Marvin M2Added most receptors, and connected parts where possible. Still work needs to be done
103306view16:35, 21 February 2019Marvin M2New pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AGTR1GeneProductAGTR1 (HGNC)
AGTR2GeneProductAGTR2 (HGNC)
AKT1S1GeneProductAKT1S1 (HGNC)
CNTFRGeneProduct1271 (Entrez Gene) CNTFR,CT-1R,ycsubunit)
CREBBPGeneProductCREBBP (HGNC)
CSF2RAGeneProductCSF2RA (HGNC)
CSF2RBGeneProductCSF2RB (HGNC)
CSF3RGeneProduct1441 (Entrez Gene) G-CSFR
CTF1GeneProductCTF1 (HGNC)
DEPTORGeneProductDEPTOR (HGNC)
DUSP2GeneProduct1844 (Entrez Gene) DUSP2
EGFRGeneProduct1956 (Entrez Gene) GM-CSFR(homodimericIL-20R,IL-22R,EGFR,PDGFR
F2RGeneProductF2R (HGNC)
F2RL2GeneProductF2RL2 (HGNC)
F2RL3GeneProductF2RL3 (HGNC)
GHRGeneProduct2690 (Entrez Gene) GHR,
IFNAR1GeneProduct3454 (Entrez Gene) IFNAR,IFNGR,
IFNAR2GeneProductIFNAR2 (HGNC)
IFNGR1GeneProductIFNGR1 (HGNC)
IFNGR2GeneProductIFNGR2 (HGNC)
IFNLR1GeneProductIFNLR1 (HGNC)
IL10RAGeneProductIL10RA (HGNC)
IL10RBGeneProductIL10RB (HGNC)
IL11RAGeneProductIL11RA (HGNC)
IL12RB2GeneProductIL12RB2 (HGNC)
IL15RAGeneProductIL15RA (HGNC)
IL20RAGeneProductIL20RA (HGNC)
IL20RBGeneProductIL20RB (HGNC)
IL21RGeneProduct50615 (Entrez Gene) IL-21R
IL22RA1GeneProductIL22RA1 (HGNC)
IL27RAGeneProduct9466 (Entrez Gene) IL-27R,IL-35R,IL-21R(sharedsubunit)
IL2RAGeneProduct3559 (Entrez Gene) IL-2R,IL-7R,
IL2RBGeneProductIL2RB (HGNC)
IL2RGGeneProductIL2RG (HGNC)
IL3RAGeneProductIL3RA (HGNC)
IL5RAGeneProductIL5RA (HGNC)
IL6RGeneProduct3570 (Entrez Gene) IL-6R,
IL6STGeneProductIL6ST (HGNC)
IL7RGeneProduct3575 (Entrez Gene) IL-7R,
IL9RGeneProduct3581 (Entrez Gene) IL-9R,
JAK1GeneProductJAK1 (HGNC)
JAK2GeneProductJAK2 (HGNC)
JAK3GeneProductJAK3 (HGNC)
LIFRGeneProduct3977 (Entrez Gene) LIFR,OSMR
MAPK10GeneProduct5602 (Entrez Gene) MAPK
MAPK11GeneProduct5600 (Entrez Gene) MAPK
MAPK12GeneProduct6300 (Entrez Gene) MAPK
MAPK13GeneProduct5603 (Entrez Gene) MAPK
MAPK14GeneProduct1432 (Entrez Gene) MAPK
MAPK1GeneProduct5594 (Entrez Gene) MAPK
MAPK15GeneProductMAPK15 (HGNC)
MAPK3GeneProduct5595 (Entrez Gene) MAPK
MAPK4GeneProductMAPK4 (HGNC)
MAPK6GeneProductMAPK6 (HGNC)
MAPK7GeneProductMAPK7 (HGNC)
MAPK8GeneProduct5599 (Entrez Gene) MAPK
MAPK9GeneProduct5601 (Entrez Gene) MAPK
MAPKAP1GeneProductMAPKAP1 (HGNC)
MLST8GeneProductMLST8 (HGNC)
MPLGeneProduct4352 (Entrez Gene) TpoR,
MTORGeneProductMTOR (HGNC)
OSMRGeneProduct9180 (Entrez Gene) OSMR
PDGFRAGeneProductPDGFRA (HGNC)
PDGFRBGeneProductPDGFRB (HGNC)
PIAS3GeneProduct10401 (Entrez Gene) PIAS3
PRKCBGeneProductPRKCB (HGNC)
PTPRCGeneProduct5788 (Entrez Gene) PTPRC
PTPRDGeneProductPTPRD (HGNC)
PTPRTGeneProduct11122 (Entrez Gene) PTPRT
RICTORGeneProductRICTOR (HGNC)
RPTORGeneProductRPTOR (HGNC)
SETD7GeneProductSETD7 (HGNC)
SOCS3GeneProduct9021 (Entrez Gene) SOCS3
SRCGeneProductSRC (HGNC)
STAT3GeneProduct6774 (Entrez Gene) STAT3
STMN1GeneProductSTMN1 (HGNC)
TRIM28GeneProductTRIM28 (HGNC)
TYK2GeneProductTYK2 (HGNC)

Annotated Interactions

No annotated interactions

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