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Home > Curated Information Page > PubMed Id: 16354680
Tzatsos A, Kandror KV (2006) Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol Cell Biol 26, 63-76 16354680
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.
Information from this record has been curated, but not yet edited in PhosphoSitePlus® and may be incomplete.
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S65-p - 4E-BP1 (human)
Modsite: FLMECrNsPVtktPP SwissProt Entrez-Gene
Orthologous residues
4E‑BP1 (human): S65‑p, 4E‑BP1 (mouse): S64‑p, 4E‑BP1 (rat): S64‑p, 4E‑BP1 (fruit fly): S65‑p, 4E‑BP1 (cow): S65‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  3T3-L1 (fibroblast), HepG2 (hepatic), L6 (myoblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse, rat
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
metformin insulin inhibit treatment-induced increase

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:  3T3-L1 (fibroblast), HepG2 (hepatic), L6 (myoblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse, rat
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
rapamycin insulin inhibit treatment-induced increase
metformin insulin inhibit treatment-induced increase
leucine insulin augment treatment-induced increase
siRNA insulin inhibit treatment-induced increase Raptor siRNA
RHEB (human) increase
glucose increase
TNF no change compared to control

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:  3T3-L1 (fibroblast), HepG2 (hepatic), L6 (myoblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse, rat
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
rapamycin insulin augment treatment-induced increase
metformin insulin augment treatment-induced increase
siRNA increase Raptor siRNA
TNF no change compared to control

T183-p - AMPKA1 (rat)
Modsite: SDGEFLRtsCGSPNY SwissProt Entrez-Gene
Orthologous residues
AMPKA1 (human): T183‑p, AMPKA1 iso2 (human): T198‑p, AMPKA1 (mouse): T183‑p, AMPKA1 (rat): T183‑p, AMPKA1 (fruit fly): T184‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  3T3-L1 (fibroblast), HepG2 (hepatic), L6 (myoblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse, rat
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
glucose decrease
insulin no change compared to control
2-deoxyglucose insulin increase
metformin insulin increase
metformin increase

T203-p - ERK1 (rat)
Modsite: HDHTGFLtEyVAtRW SwissProt Entrez-Gene
Orthologous residues
ERK1 (human): T202‑p, ERK1 iso2 (human): T202‑p, ERK1 iso3 (human): T202‑p, ERK1 (mouse): T203‑p, ERK1 (rat): T203‑p, ERK1 (hamster): T192‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  3T3-L1 (fibroblast), HepG2 (hepatic), L6 (myoblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse, rat
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
rapamycin insulin no effect upon treatment-induced increase
metformin insulin no effect upon treatment-induced increase

Y205-p - ERK1 (rat)
Modsite: HTGFLtEyVAtRWYR SwissProt Entrez-Gene
Orthologous residues
ERK1 (human): Y204‑p, ERK1 iso2 (human): Y204‑p, ERK1 iso3 (human): Y204‑p, ERK1 (mouse): Y205‑p, ERK1 (rat): Y205‑p, ERK1 (hamster): Y194‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  3T3-L1 (fibroblast), HepG2 (hepatic), L6 (myoblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse, rat
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
rapamycin insulin no effect upon treatment-induced increase
metformin insulin no effect upon treatment-induced increase

T183-p - ERK2 (rat)
Modsite: HDHtGFLtEyVAtRW SwissProt Entrez-Gene
Orthologous residues
ERK2 (human): T185‑p, ERK2 (mouse): T183‑p, ERK2 (rat): T183‑p, ERK2 (chicken): T193‑p, ERK2 (cow): T185‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  3T3-L1 (fibroblast), HepG2 (hepatic), L6 (myoblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse, rat
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
rapamycin insulin no effect upon treatment-induced increase
metformin insulin no effect upon treatment-induced increase

Y185-p - ERK2 (rat)
Modsite: HtGFLtEyVAtRWYR SwissProt Entrez-Gene
Orthologous residues
ERK2 (human): Y187‑p, ERK2 (mouse): Y185‑p, ERK2 (rat): Y185‑p, ERK2 (chicken): Y195‑p, ERK2 (cow): Y187‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  3T3-L1 (fibroblast), HepG2 (hepatic), L6 (myoblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse, rat
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
rapamycin insulin no effect upon treatment-induced increase
metformin insulin no effect upon treatment-induced increase

S21-p - GSK3A (rat)
Modsite: SGRARtssFAEPGGG SwissProt Entrez-Gene
Orthologous residues
GSK3A (human): S21‑p, GSK3A (mouse): S21‑p, GSK3A (rat): S21‑p, GSK3A (cow): S21‑p
Characterization
Methods used to characterize site in vivo phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  3T3-L1 (fibroblast), HepG2 (hepatic), L6 (myoblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse, rat
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
rapamycin insulin augment treatment-induced increase

S612-p - IRS1 (rat)
Modsite: DDGyMPMsPGVAPVP SwissProt Entrez-Gene
Orthologous residues
IRS1 (human): S616‑p, IRS1 (mouse): S612‑p, IRS1 (rat): S612‑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-L1 (fibroblast), HepG2 (hepatic), L6 (myoblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse, rat
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
Downstream Regulation
Effect of modification (function):  molecular association, regulation
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
PIK3R1 (rat) Disrupts co-immunoprecipitation

S632-p - IRS1 (rat)
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 mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  liver cancer
Relevant cell lines - cell types - tissues:  293 (epithelial), 3T3-L1 (fibroblast), HepG2 (hepatic), L6 (myoblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse, rat
Enzymes shown to modify site in vitro
Type Enzyme
KINASE mTOR (human)
Comments:  mTOR/Raptor
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
rapamycin insulin inhibit treatment-induced increase
metformin insulin inhibit treatment-induced increase
leucine insulin augment treatment-induced increase
siRNA insulin inhibit treatment-induced increase Raptor siRNA
insulin increase
2-deoxyglucose insulin inhibit treatment-induced increase
glucose increase
RHEB (human) increase
LKB1 (human) RHEB (human) inhibit treatment-induced increase
TNF no change compared to control
Downstream Regulation
Effect of modification (function):  molecular association, regulation
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
PIK3R1 (rat) Disrupts co-immunoprecipitation

S635-p - IRS1 (rat)
Modsite: yMPMsPKsVsAPQQI SwissProt Entrez-Gene
Orthologous residues
IRS1 (human): S639‑p, IRS1 (mouse): S635‑p, IRS1 (rat): S635‑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-L1 (fibroblast), HepG2 (hepatic), L6 (myoblast)
Cellular systems studied:  cell lines
Species studied:  human, mouse, rat
Enzymes shown to modify site in vitro
Type Enzyme
KINASE mTOR (human)
Comments:  mTOR/Raptor
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
rapamycin insulin inhibit treatment-induced increase
metformin insulin inhibit treatment-induced increase
leucine insulin augment treatment-induced increase
siRNA insulin inhibit treatment-induced increase Raptor siRNA
insulin increase
2-deoxyglucose insulin inhibit treatment-induced increase
glucose increase
RHEB (human) increase
LKB1 (human) RHEB (human) inhibit treatment-induced increase
TNF no change compared to control
Downstream Regulation
Effect of modification (function):  molecular association, regulation
Modification regulates interactions with: 
Interacting molecule Interacting domains Effect Consequences (function) Consequences (process) Detection assays
PIK3R1 (rat) Disrupts co-immunoprecipitation