Curated Information
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Home > Curated Information Page > PubMed Id: 18952604
Zhang J, et al. (2008) S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2. J Biol Chem 283, 35375-82 18952604
This page summarizes selected information from the record referenced above and curated into PhosphoSitePlus®, a comprehensive online resource for the study of protein post-translational modifications (NAR, 2015, 43:D512-20). To learn more about the scope of PhosphoSitePlus®, click here.
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S270-p - IRS1 (human)
Modsite: EFRPRsKsQSssNCs SwissProt Entrez-Gene
Orthologous residues
IRS1 (human): S270‑p, IRS1 (mouse): S265‑p, IRS1 (rat): S265‑p
Characterization
Methods used to characterize site in vivo mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), 3T3 (fibroblast), 3T3-L1 (fibroblast), H4IIe (hepatic)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE p70S6K (human)
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE p70S6K (human) mutation in upstream enzyme recognition motif, pharmacological activator of upstream enzyme, transfection of wild-type enzyme, siRNA inhibition of enzyme, transfection of dominant-negative enzyme, co-immunoprecipitation

S307-p - IRS1 (human)
Modsite: TRRsRtEsItAtsPA SwissProt Entrez-Gene
Orthologous residues
IRS1 (human): S307‑p, IRS1 (mouse): S302‑p, IRS1 (rat): S302‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), 3T3 (fibroblast), 3T3-L1 (fibroblast), H4IIe (hepatic)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE p70S6K (human)
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE p70S6K (human) mutation in upstream enzyme recognition motif, pharmacological activator of upstream enzyme, transfection of wild-type enzyme, siRNA inhibition of enzyme, transfection of dominant-negative enzyme, co-immunoprecipitation

S636-p - IRS1 (human)
Modsite: sGDyMPMsPKsVSAP SwissProt Entrez-Gene
Orthologous residues
IRS1 (human): S636‑p, IRS1 (mouse): S632‑p, IRS1 (rat): S632‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), 3T3 (fibroblast), 3T3-L1 (fibroblast), H4IIe (hepatic)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE p70S6K (human)
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE p70S6K (human) mutation in upstream enzyme recognition motif, pharmacological activator of upstream enzyme, transfection of wild-type enzyme, siRNA inhibition of enzyme, transfection of dominant-negative enzyme, co-immunoprecipitation

S1101-p - IRS1 (human)
Modsite: GCRRRHssEtFsStP SwissProt Entrez-Gene
Orthologous residues
IRS1 (human): S1101‑p, IRS1 (mouse): S1097‑p, IRS1 (rat): S1100‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), 3T3 (fibroblast), 3T3-L1 (fibroblast), H4IIe (hepatic)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE p70S6K (human)
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE p70S6K (human) mutation in upstream enzyme recognition motif, pharmacological activator of upstream enzyme, transfection of wild-type enzyme, siRNA inhibition of enzyme, transfection of dominant-negative enzyme, co-immunoprecipitation

S265-p - IRS1 (mouse)
Modsite: EFRPRSKsQssSsCs SwissProt Entrez-Gene
Orthologous residues
IRS1 (human): S270‑p, IRS1 (mouse): S265‑p, IRS1 (rat): S265‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), 3T3 (fibroblast), 3T3-L1 (fibroblast), H4IIe (hepatic)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
TNF increase
Associated Diseases
Diseases Alterations Comments
obesity, hyperphagic increased ob/ob mice

S302-p - IRS1 (mouse)
Modsite: TRRSRtEsITAtsPA SwissProt Entrez-Gene
Orthologous residues
IRS1 (human): S307‑p, IRS1 (mouse): S302‑p, IRS1 (rat): S302‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), 3T3 (fibroblast), 3T3-L1 (fibroblast), H4IIe (hepatic)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Associated Diseases
Diseases Alterations Comments
obesity, hyperphagic increased ob/ob mice

S632-p - IRS1 (mouse)
Modsite: NGDyMPMsPKsVsAP SwissProt Entrez-Gene
Orthologous residues
IRS1 (human): S636‑p, IRS1 (mouse): S632‑p, IRS1 (rat): S632‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), 3T3 (fibroblast), 3T3-L1 (fibroblast), H4IIe (hepatic)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Associated Diseases
Diseases Alterations Comments
obesity, hyperphagic increased ob/ob mice

S1097-p - IRS1 (mouse)
Modsite: GCRRRHssEtFSAPt SwissProt Entrez-Gene
Orthologous residues
IRS1 (human): S1101‑p, IRS1 (mouse): S1097‑p, IRS1 (rat): S1100‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), 3T3 (fibroblast), 3T3-L1 (fibroblast), H4IIe (hepatic)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Associated Diseases
Diseases Alterations Comments
obesity, hyperphagic increased ob/ob mice

T412-p - p70S6K (mouse)
Modsite: NQVFLGFtYVAPSVL SwissProt Entrez-Gene
Orthologous residues
p70S6K (human): T412‑p, p70S6K iso2 (human): T389‑p, p70S6K (mouse): T412‑p, p70S6K (rat): T412‑p, p70S6K iso2 (rat): T389‑p, p70S6K (fruit fly): T398‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), 3T3 (fibroblast), 3T3-L1 (fibroblast), H4IIe (hepatic)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
TNF increase
TNF increase
wortmannin TNF no effect upon treatment-induced increase
rapamycin TNF inhibit treatment-induced increase
15d-PGJ2 TNF inhibit treatment-induced increase
TNF IKKB (human) increase
Associated Diseases
Diseases Alterations Comments
obesity, hyperphagic increased ob/ob mice

T308-p - Akt1 (rat)
Modsite: KDGATMKtFCGTPEy SwissProt Entrez-Gene
Orthologous residues
Akt1 (human): T308‑p, Akt1 iso2 (human): T246‑p, Akt1 (mouse): T308‑p, Akt1 (rat): T308‑p, Akt1 (fruit fly): T423‑p, Akt1 (cow): T308‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), 3T3 (fibroblast), 3T3-L1 (fibroblast), H4IIe (hepatic)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
TNF increase
insulin increase
TNF insulin inhibit treatment-induced increase

S473-p - Akt1 (rat)
Modsite: RPHFPQFsYSASGTA SwissProt Entrez-Gene
Orthologous residues
Akt1 (human): S473‑p, Akt1 iso2 (human): S411‑p, Akt1 (mouse): S473‑p, Akt1 (rat): S473‑p, Akt1 (fruit fly): S586‑p, Akt1 (cow): S473‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), 3T3 (fibroblast), 3T3-L1 (fibroblast), H4IIe (hepatic)
Cellular systems studied:  cell lines
Species studied:  human, mouse
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
TNF increase