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Home > Curated Information Page > PubMed Id: 17386267
Brognard J, Sierecki E, Gao T, Newton AC (2007) PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. Mol Cell 25, 917-31 17386267
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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T308-p - Akt1 (human)
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
Upstream Regulation
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
siRNA PHLPP (human) no change compared to control
siRNA PHLPP2 (human) no change compared to control
siRNA PHLPP2 (human) no change compared to control
EGF increase
siRNA EGF PHLPP (human) augment treatment-induced increase
siRNA EGF PHLPP2 (human) augment treatment-induced increase

S473-p - Akt1 (human)
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
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
PHOSPHATASE PHLPP2 (human) siRNA inhibition of enzyme, co-immunoprecipitation, phospho-antibody, transfection of wild-type enzyme
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
siRNA PHLPP2 (human) increase
siRNA PHLPP (human) no change compared to control
PHLPP2 (human) decrease
EGF increase
siRNA EGF PHLPP (human) augment treatment-induced increase
siRNA EGF PHLPP2 (human) augment treatment-induced increase

T309-p - Akt2 (human)
Modsite: sDGAtMKtFCGtPEy SwissProt Entrez-Gene
Orthologous residues
Akt2 (human): T309‑p, Akt2 (mouse): T309‑p, Akt2 (rat): T309‑p

S474-p - Akt2 (human)
Modsite: RTHFPQFsysAsIRE SwissProt Entrez-Gene
Orthologous residues
Akt2 (human): S474‑p, Akt2 (mouse): S474‑p, Akt2 (rat): S474‑p
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
PHOSPHATASE PHLPP (human) siRNA inhibition of enzyme, co-immunoprecipitation, phospho-antibody
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
siRNA PHLPP (human) increase
siRNA PHLPP2 (human) no change compared to control

T305-p - Akt3 (human)
Modsite: tDAAtMKtFCGtPEy SwissProt Entrez-Gene
Orthologous residues
Akt3 (human): T305‑p, Akt3 (mouse): T305‑p, Akt3 (rat): T305‑p

S472-p - Akt3 (human)
Modsite: RPHFPQFsysAsGRE SwissProt Entrez-Gene
Orthologous residues
Akt3 (human): S472‑p, Akt3 (mouse): S472‑p, Akt3 (rat): S472‑p
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
PHOSPHATASE PHLPP (human) siRNA inhibition of enzyme, co-immunoprecipitation, phospho-antibody
PHOSPHATASE PHLPP2 (human) siRNA inhibition of enzyme, co-immunoprecipitation, phospho-antibody, transfection of wild-type enzyme
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
siRNA PHLPP (human) increase
siRNA PHLPP2 (human) increase

T24-p - FOXO1A (human)
Modsite: LPRPRSCtWPLPRPE SwissProt Entrez-Gene
Orthologous residues
FOXO1A (human): T24‑p, FOXO1A (mouse): T24‑p, FOXO1A (rat): T24‑p
Characterization
Methods used to characterize site in vivo mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  breast cancer, lung cancer, non-small cell lung cancer
Relevant cell lines - cell types - tissues:  BT-474 (breast cell), HEK293T (epithelial), Hs 578T (breast cell), MCF-7 (breast cell), MDA-MB-231 (breast cell), NCI-H157 (pulmonary), SKBr3 (breast cell), ZR-75-1 (breast cell)
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
siRNA PHLPP (human) increase
siRNA PHLPP2 (human) increase
siRNA Akt1 (human) decrease
siRNA Akt2 (human) decrease
siRNA Akt3 (human) decrease

S21-p - GSK3A (human)
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 mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  breast cancer, lung cancer, non-small cell lung cancer
Relevant cell lines - cell types - tissues:  BT-474 (breast cell), HEK293T (epithelial), Hs 578T (breast cell), MCF-7 (breast cell), MDA-MB-231 (breast cell), NCI-H157 (pulmonary), SKBr3 (breast cell), ZR-75-1 (breast cell)
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
siRNA PHLPP (human) increase
siRNA PHLPP2 (human) no change compared to control
siRNA Akt1 (human) no change compared to control
siRNA Akt2 (human) decrease
siRNA Akt3 (human) no change compared to control

S9-p - GSK3B (human)
Modsite: SGRPRttsFAEsCkP SwissProt Entrez-Gene
Orthologous residues
GSK3B (human): S9‑p, GSK3B iso2 (human): S9‑p, GSK3B (mouse): S9‑p, GSK3B (rat): S9‑p, GSK3B (rabbit): S9‑p
Characterization
Methods used to characterize site in vivo mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  breast cancer, lung cancer, non-small cell lung cancer
Relevant cell lines - cell types - tissues:  BT-474 (breast cell), HEK293T (epithelial), Hs 578T (breast cell), MCF-7 (breast cell), MDA-MB-231 (breast cell), NCI-H157 (pulmonary), SKBr3 (breast cell), ZR-75-1 (breast cell)
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
siRNA PHLPP (human) increase
siRNA PHLPP2 (human) increase
siRNA Akt1 (human) decrease
siRNA Akt2 (human) decrease
siRNA Akt3 (human) decrease

S166-p - MDM2 (human)
Modsite: SsRRRAIsEtEENsD SwissProt Entrez-Gene
Orthologous residues
MDM2 (human): S166‑p, MDM2 (mouse): S163‑p, MDM2 (rat): S138‑p
Characterization
Methods used to characterize site in vivo mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  breast cancer, lung cancer, non-small cell lung cancer
Relevant cell lines - cell types - tissues:  BT-474 (breast cell), HEK293T (epithelial), Hs 578T (breast cell), MCF-7 (breast cell), MDA-MB-231 (breast cell), NCI-H157 (pulmonary), SKBr3 (breast cell), ZR-75-1 (breast cell)
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
siRNA PHLPP (human) increase
siRNA PHLPP2 (human) no change compared to control
siRNA Akt1 (human) no change compared to control
siRNA Akt2 (human) decrease
siRNA Akt3 (human) no change compared to control

T157-p - p27Kip1 (human)
Modsite: GIRkrPAtDDSSTQN SwissProt Entrez-Gene
Orthologous residues
p27Kip1 (human): T157‑p, p27Kip1 (mouse): A157‑p, p27Kip1 (rat): A157‑p
Characterization
Methods used to characterize site in vivo mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  breast cancer, lung cancer, non-small cell lung cancer
Relevant cell lines - cell types - tissues:  BT-474 (breast cell), HEK293T (epithelial), Hs 578T (breast cell), MCF-7 (breast cell), MDA-MB-231 (breast cell), NCI-H157 (pulmonary), SKBr3 (breast cell), ZR-75-1 (breast cell)
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
siRNA PHLPP (human) no change compared to control
siRNA PHLPP2 (human) increase
siRNA Akt1 (human) no change compared to control
siRNA Akt2 (human) no change compared to control
siRNA Akt3 (human) decrease

S939-p - TSC2 (human)
Modsite: sFRARstsLNERPKs SwissProt Entrez-Gene
Orthologous residues
TSC2 (human): S939‑p, TSC2 iso2 (human): S939‑p, TSC2 iso3 (human): S939‑p, TSC2 iso4 (human): S939‑p, TSC2 (mouse): S939‑p, TSC2 iso6 (mouse): S939‑p, TSC2 (rat): S939‑p, TSC2 iso2 (rat): S939‑p
Characterization
Methods used to characterize site in vivo mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  breast cancer, lung cancer, non-small cell lung cancer
Relevant cell lines - cell types - tissues:  BT-474 (breast cell), HEK293T (epithelial), Hs 578T (breast cell), MCF-7 (breast cell), MDA-MB-231 (breast cell), NCI-H157 (pulmonary), SKBr3 (breast cell), ZR-75-1 (breast cell)
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
siRNA PHLPP (human) increase
siRNA PHLPP2 (human) increase
siRNA Akt1 (human) decrease
siRNA Akt2 (human) decrease
siRNA Akt3 (human) no change compared to control

T1462-p - TSC2 (human)
Modsite: GLRPRGytISDsAPs SwissProt Entrez-Gene
Orthologous residues
TSC2 (human): T1462‑p, TSC2 iso2 (human): T1419‑p, TSC2 iso3 (human): T1418‑p, TSC2 iso4 (human): T1439‑p, TSC2 (mouse): T1465‑p, TSC2 iso6 (mouse): T1443‑p, TSC2 (rat): T1466‑p, TSC2 iso2 (rat): T1423‑p
Characterization
Methods used to characterize site in vivo mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  breast cancer, lung cancer, non-small cell lung cancer
Relevant cell lines - cell types - tissues:  BT-474 (breast cell), HEK293T (epithelial), Hs 578T (breast cell), MCF-7 (breast cell), MDA-MB-231 (breast cell), NCI-H157 (pulmonary), SKBr3 (breast cell), ZR-75-1 (breast cell)
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
siRNA PHLPP (human) increase
siRNA PHLPP2 (human) increase
siRNA Akt1 (human) decrease
siRNA Akt2 (human) decrease
siRNA Akt3 (human) decrease