Curated Information
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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, 2012,40:D261-70). 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.
Only sites from this record are displayed on this page. Click on the protein name to open the protein page, and on the RSD number to open the site page. For the complete dataset, click the download button, on the right.
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S65-p - 4E-BP1 (human)
Orthologous residues
4E‑BP1 (human): S65‑p, 4E‑BP1 (mouse): S64‑p, 4E‑BP1 (rat): S64‑p, 4E‑BP1 (fruit fly): 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)
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)
Orthologous residues
Akt1 (human): T308‑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)
Orthologous residues
AMPKA1 (human): T183‑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)
Orthologous residues
ERK1 (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)
Orthologous residues
ERK1 (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)
Orthologous residues
ERK2 (human): T185‑p, ERK2 (mouse): T183‑p, ERK2 (rat): T183‑p, ERK2 (chicken): T193‑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)
Orthologous residues
ERK2 (human): Y187‑p, ERK2 (mouse): Y185‑p, ERK2 (rat): Y185‑p, ERK2 (chicken): Y195‑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)
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)
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)
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)
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


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