Curated Information
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Curated Information Page
PubMed Id: 16959574 
Inoki K, et al. (2006) TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell 126, 955-68 16959574
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.
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.
Download Sites

S9-p - GSK3B (human)
Orthologous residues
GSK3B (human): S9‑p, GSK3B iso2 (human): S9‑p, GSK3B (mouse): S9‑p, GSK3B (rat): S9‑p, GSK3B (rabbit): S3‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  293 (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  human
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
glucose starvation decrease

S473-p - Akt1 (mouse)
Orthologous residues
Akt1 (human): S473‑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
 Relevant cell lines - cell types - tissues:  MEF (fibroblast), Rat1 (fibroblast), RIE (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  mouse, rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
Wnt no change compared to control
rapamycin no change compared to control
U0126 no change compared to control
wortmannin decrease
Wnt3a no change compared to control
insulin increase
lithium no change compared to control
NaCl no change compared to control

T183-p - AMPKA1 (mouse)
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
 Relevant cell lines - cell types - tissues:  293 (epithelial), MEF (fibroblast), ST2 (stromal)
 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
Wnt3a no change compared to control
rapamycin no change compared to control
wortmannin no change compared to control
glucose starvation increase
2-deoxyglucose increase
medium change decrease
compound C decrease
AICAR 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
 Relevant cell lines - cell types - tissues:  293 (epithelial), C2C12 (myoblast), MC3T3-E1 (preosteoblast), MEF (fibroblast), Rat1 (fibroblast), RIE (epithelial), ST2 (stromal)
 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
Wnt increase
rapamycin Wnt inhibit treatment-induced increase
wortmannin Wnt inhibit treatment-induced increase
U0126 Wnt no effect upon treatment-induced increase
rapamycin decrease
wortmannin decrease
Wnt3a increase
rapamycin Wnt3a inhibit treatment-induced increase
wortmannin Wnt3a inhibit treatment-induced increase
Wnt3a DKK1 (human) inhibit treatment-induced increase
DKK1 (human) no change compared to control
insulin increase
Wnt10b increase
rapamycin Wnt10b inhibit treatment-induced increase
siRNA increase GSK3a + GSK3b RNAi
glucose starvation decrease
lithium increase
NaCl no change compared to control
siRNA increase TSC2 RNAi
AICAR decrease
Wnt3a AICAR inhibit treatment-induced decrease

S240-p - S6 (mouse)
Orthologous residues
S6 (human): S240‑p, S6 (mouse): S240‑p, S6 (rat): S240‑p, S6 (fruit fly): S239‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  293 (epithelial), MEF (fibroblast), ST2 (stromal)
 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
Wnt3a increase
rapamycin Wnt3a inhibit treatment-induced increase
wortmannin Wnt3a inhibit treatment-induced increase
rapamycin decrease
wortmannin decrease
Wnt10b increase
rapamycin Wnt10b inhibit treatment-induced increase
lithium increase

S244-p - S6 (mouse)
Orthologous residues
S6 (human): S244‑p, S6 (mouse): S244‑p, S6 (rat): S244‑p, S6 (fruit fly): V243‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  293 (epithelial), MEF (fibroblast), ST2 (stromal)
 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
Wnt3a increase
rapamycin Wnt3a inhibit treatment-induced increase
wortmannin Wnt3a inhibit treatment-induced increase
rapamycin decrease
wortmannin decrease
Wnt10b increase
rapamycin Wnt10b inhibit treatment-induced increase
lithium increase

T1373-p - TSC2 (rat)
Orthologous residues
TSC2 (human): S1371‑p, TSC2 iso3 (human): S1327‑p, TSC2 iso4 (human): S1348‑p, TSC2 (mouse): A1372‑p, TSC2 iso6 (mouse): A1350‑p, TSC2 (rat): T1373‑p, TSC2 iso2 (rat): T1330‑p
Characterization
 Methods used to characterize site in vivo 2D analysis, [32P] bio-synthetic labeling, phosphopeptide mapping
 Relevant cell lines - cell types - tissues:  293 (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  human
 Enzymes shown to modify site in vitro
Type Enzyme
KINASE GSK3B (human)
 Comments:  Requires prior priming phosphorylation of S1389 by APMK1 (in vitro)
Upstream Regulation
 Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE GSK3B (human) phospho-antibody, transfection of wild-type enzyme, genetic knockout/knockin of upstream enzyme, pharmacological activator of upstream enzyme, modification site within consensus motif, co-immunoprecipitation
 Comments:  Co-IP shown in other paper.
Downstream Regulation
 Effect of modification (function):  activity, inhibited, phosphorylation
 Effect of modification (process):  apoptosis, inhibited, translation, altered
 Comments:  inhibits mTOR signaling. required for Wnt-3a to stimulation phosphorylation of S6K and 4EBP1 and increase protein levels of cyclin D1 and VEGF (cyclin D1 through translation not transcription).

S1377-p - TSC2 (rat)
Orthologous residues
TSC2 (human): S1375‑p, TSC2 iso3 (human): S1331‑p, TSC2 iso4 (human): S1352‑p, TSC2 (mouse): S1376‑p, TSC2 iso6 (mouse): S1354‑p, TSC2 (rat): S1377‑p, TSC2 iso2 (rat): S1334‑p
Characterization
 Methods used to characterize site in vivo 2D analysis, [32P] bio-synthetic labeling, phosphopeptide mapping
 Relevant cell lines - cell types - tissues:  293 (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  human
 Enzymes shown to modify site in vitro
Type Enzyme
KINASE GSK3B (human)
 Comments:  Requires prior priming phosphorylation of S1389 by APMK1 (in vitro)
Upstream Regulation
 Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE GSK3B (human) phospho-antibody, transfection of wild-type enzyme, genetic knockout/knockin of upstream enzyme, pharmacological activator of upstream enzyme, modification site within consensus motif, co-immunoprecipitation
 Comments:  Co-IP shown in other paper.
Downstream Regulation
 Effect of modification (function):  activity, inhibited, phosphorylation
 Effect of modification (process):  apoptosis, inhibited, translation, altered
 Comments:  inhibits mTOR signaling. required for Wnt-3a to stimulation phosphorylation of S6K and 4EBP1 and increase protein levels of cyclin D1 and VEGF (cyclin D1 through translation not transcription).

S1381-p - TSC2 (rat)
Orthologous residues
TSC2 (human): S1379‑p, TSC2 iso3 (human): S1335‑p, TSC2 iso4 (human): S1356‑p, TSC2 (mouse): S1380‑p, TSC2 iso6 (mouse): S1358‑p, TSC2 (rat): S1381‑p, TSC2 iso2 (rat): S1338‑p
Characterization
 Methods used to characterize site in vivo 2D analysis, [32P] bio-synthetic labeling, phospho-antibody, phosphopeptide mapping, western blotting
 Relevant cell lines - cell types - tissues:  293 (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  human
 Enzymes shown to modify site in vitro
Type Enzyme
KINASE GSK3B (human)
 Comments:  Requires prior priming phosphorylation of S1389 by APMK1 (in vitro)
Upstream Regulation
 Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE GSK3B (human) phospho-antibody, transfection of wild-type enzyme, genetic knockout/knockin of upstream enzyme, pharmacological activator of upstream enzyme, modification site within consensus motif, co-immunoprecipitation
 Comments:  Co-IP shown in other paper.
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
2-deoxyglucose increase
compound C 2-deoxyglucose inhibit treatment-induced increase
Downstream Regulation
 Effect of modification (function):  activity, inhibited, phosphorylation
 Effect of modification (process):  apoptosis, inhibited, translation, altered
 Comments:  inhibits mTOR signaling. required for Wnt-3a to stimulation phosphorylation of S6K and 4EBP1 and increase protein levels of cyclin D1 and VEGF (cyclin D1 through translation not transcription).

S1385-p - TSC2 (rat)
Orthologous residues
TSC2 (human): S1383‑p, TSC2 iso3 (human): S1339‑p, TSC2 iso4 (human): S1360‑p, TSC2 (mouse): S1384‑p, TSC2 iso6 (mouse): S1362‑p, TSC2 (rat): S1385‑p, TSC2 iso2 (rat): S1342‑p
Characterization
 Methods used to characterize site in vivo 2D analysis, [32P] bio-synthetic labeling, phospho-antibody, phosphopeptide mapping, western blotting
 Relevant cell lines - cell types - tissues:  293 (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  human
 Enzymes shown to modify site in vitro
Type Enzyme
KINASE GSK3B (human)
 Comments:  Requires prior priming phosphorylation of S1389 by APMK1 (in vitro)
Upstream Regulation
 Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE GSK3B (human) phospho-antibody, transfection of wild-type enzyme, genetic knockout/knockin of upstream enzyme, pharmacological activator of upstream enzyme, modification site within consensus motif, co-immunoprecipitation
 Comments:  Co-IP shown in other paper.
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
2-deoxyglucose increase
compound C 2-deoxyglucose inhibit treatment-induced increase
Downstream Regulation
 Effect of modification (function):  activity, inhibited, phosphorylation
 Effect of modification (process):  apoptosis, inhibited, translation, altered
 Comments:  inhibits mTOR signaling. required for Wnt-3a to stimulation phosphorylation of S6K and 4EBP1 and increase protein levels of cyclin D1 and VEGF (cyclin D1 through translation not transcription).

S1389-p - TSC2 (rat)
Orthologous residues
TSC2 (human): S1387‑p, TSC2 iso3 (human): S1343‑p, TSC2 iso4 (human): S1364‑p, TSC2 (mouse): S1388‑p, TSC2 iso6 (mouse): S1366‑p, TSC2 (rat): S1389‑p, TSC2 iso2 (rat): S1346‑p
Characterization
 Enzymes shown to modify site in vitro
Type Enzyme
KINASE AMPKA1 (human)


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