Li X, Liu J, Gao T (2009) beta-TrCP-mediated ubiquitination and degradation of PHLPP1 are negatively regulated by Akt. Mol Cell Biol 29, 6192-205 19797085

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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 Characterization Methods used to characterize site in vivo:  phospho-antibody, western blotting Relevant cell lines - cell types - tissues:  HEK293T (epithelial) Cellular systems studied:  cell lines Species studied:  human Downstream Regulation Effect of modification (function):  protein degradation Comments:  PHLPP phosphorylation induces degradation and Akt1 activation negatively regulates degradation.

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:  phospho-antibody, western blotting Relevant cell lines - cell types - tissues:  HEK293T (epithelial) Cellular systems studied:  cell lines Species studied:  human

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:  phospho-antibody, western blotting Relevant cell lines - cell types - tissues:  HEK293T (epithelial) Cellular systems studied:  cell lines Species studied:  human

S1359-p - PHLPP (human) ▲

Modsite: VPRPHVQsVLLtPQD SwissProt Entrez-Gene Orthologous residues PHLPP (human): S1359‑p, PHLPP (mouse): S1315‑p, PHLPP (rat): S1322‑p Characterization Methods used to characterize site in vivo:  immunoprecipitation, mass spectrometry (in vitro), mutation of modification site, phospho-antibody, western blotting Disease tissue studied:  colorectal cancer, colorectal carcinoma Relevant cell lines - cell types - tissues:  HCT116 (intestinal), HEK293T (epithelial) Cellular systems studied:  cell lines Species studied:  human Enzymes shown to modify site in vitro:  Type Enzyme KINASE CK1A (human) KINASE GSK3B (human) Comments:  S1379 or S1381 is likely a CK1-A site and S1359 is most likely a GSK3B site, while T1363 the CK1-A priming site. Upstream Regulation Potential in vivo enzymes for site:  Type Enzyme Evidence Notes KINASE GSK3B (human) pharmacological inhibitor of upstream enzyme, phospho-antibody, transfection of wild-type enzyme, mutation in upstream enzyme recognition motif Downstream Regulation Effect of modification (function):  protein degradation Comments:  PHLPP phosphorylation induces degradation and Akt1 activation negatively regulates degradation.

T1363-p - PHLPP (human) ▲

Modsite: HVQsVLLtPQDEFFI SwissProt Entrez-Gene Orthologous residues PHLPP (human): T1363‑p, PHLPP (mouse): T1319‑p, PHLPP (rat): T1326‑p Characterization Methods used to characterize site in vivo:  immunoprecipitation, mass spectrometry (in vitro), mutation of modification site, phospho-antibody, western blotting Disease tissue studied:  colorectal cancer, colorectal carcinoma Relevant cell lines - cell types - tissues:  HCT116 (intestinal), HEK293T (epithelial) Cellular systems studied:  cell lines Species studied:  human Enzymes shown to modify site in vitro:  Type Enzyme KINASE GSK3B (human) KINASE CK1A (human) Comments:  S1379 or S1381 is likely a CK1-A site and S1359 is most likely a GSK3B site, while T1363 the CK1-A priming site. Downstream Regulation Effect of modification (function):  protein degradation Comments:  PHLPP phosphorylation induces degradation and Akt1 activation negatively regulates degradation.

S1379-p - PHLPP (human) ▲

Modsite: GSKGLWDsLsVEEAV SwissProt Entrez-Gene Orthologous residues PHLPP (human): S1379‑p, PHLPP (mouse): S1335‑p, PHLPP (rat): S1342‑p Characterization Methods used to characterize site in vivo:  immunoprecipitation, mass spectrometry (in vitro), mutation of modification site, phospho-antibody, western blotting Disease tissue studied:  colorectal cancer, colorectal carcinoma Relevant cell lines - cell types - tissues:  HCT116 (intestinal), HEK293T (epithelial) Cellular systems studied:  cell lines Species studied:  human Enzymes shown to modify site in vitro:  Type Enzyme KINASE CK1A (human) KINASE GSK3B (human) Comments:  S1379 or S1381 is likely a CK1-A site and S1359 is most likely a GSK3B site, while T1363 the CK1-A priming site.

S1381-p - PHLPP (human) ▲

Modsite: KGLWDsLsVEEAVEA SwissProt Entrez-Gene Orthologous residues PHLPP (human): S1381‑p, PHLPP (mouse): S1337‑p, PHLPP (rat): S1344‑p Characterization Methods used to characterize site in vivo:  immunoprecipitation, mass spectrometry (in vitro), mutation of modification site, phospho-antibody, western blotting Disease tissue studied:  colorectal cancer, colorectal carcinoma Relevant cell lines - cell types - tissues:  HCT116 (intestinal), HEK293T (epithelial) Cellular systems studied:  cell lines Species studied:  human Enzymes shown to modify site in vitro:  Type Enzyme KINASE CK1A (human) KINASE GSK3B (human) Comments:  S1379 or S1381 is likely a CK1-A site and S1359 is most likely a GSK3B site, while T1363 the CK1-A priming site.