Vasilcanu D, et al. (2004) The cyclolignan PPP induces activation loop-specific inhibition of tyrosine phosphorylation of the insulin-like growth factor-1 receptor. Link to the phosphatidyl inositol-3 kinase/Akt apoptotic pathway. Oncogene 23, 7854-62 15334055

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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:  mutation of modification site, phospho-antibody, western blotting Disease tissue studied:  melanoma skin cancer Relevant cell lines - cell types - tissues:  BE (melanocyte) Cellular systems studied:  cell lines Species studied:  human, mouse Comments:  P6 cells and P6 cells expressing IGF1R Upstream Regulation Treatments, proteins and their effect on site modification:  Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes IGF-1 increase picropodophyllin IGF-1 inhibit treatment-induced increase LY294002 IGF-1 inhibit treatment-induced increase

S99-p - BAD (human) ▲

Modsite: PFrGrsRsAPPNLWA SwissProt Entrez-Gene Orthologous residues BAD (human): S99‑p, BAD (mouse): S136‑p, BAD (rat): S137‑p Characterization Methods used to characterize site in vivo:  mutation of modification site, phospho-antibody, western blotting Disease tissue studied:  melanoma skin cancer Relevant cell lines - cell types - tissues:  BE (melanocyte) Cellular systems studied:  cell lines Species studied:  human, mouse Comments:  P6 cells and P6 cells expressing IGF1R Upstream Regulation Treatments, proteins and their effect on site modification:  Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes IGF-1 increase picropodophyllin IGF-1 inhibit treatment-induced increase LY294002 IGF-1 inhibit treatment-induced increase

Y1161-p - IGF1R (human) ▲

Modsite: FGMTRDIyEtDyyRk SwissProt Entrez-Gene Orthologous residues IGF1R (human): Y1161‑p, IGF1R (mouse): Y1163‑p, IGF1R (rat): Y1162‑p, IGF1R (pig): Y1161‑p Characterization Methods used to characterize site in vivo:  mutation of modification site, phospho-antibody, western blotting Disease tissue studied:  melanoma skin cancer Relevant cell lines - cell types - tissues:  BE (melanocyte) Cellular systems studied:  cell lines Species studied:  human, mouse Comments:  P6 cells and P6 cells expressing IGF1R Enzymes shown to modify site in vitro:  Type Enzyme KINASE IGF1R (human)

Y1165-p - IGF1R (human) ▲

Modsite: RDIyEtDyyRkGGkG SwissProt Entrez-Gene Orthologous residues IGF1R (human): Y1165‑p, IGF1R (mouse): Y1167‑p, IGF1R (rat): Y1166‑p, IGF1R (pig): Y1165‑p Characterization Methods used to characterize site in vivo:  mutation of modification site, phospho-antibody, western blotting Disease tissue studied:  melanoma skin cancer Relevant cell lines - cell types - tissues:  BE (melanocyte) Cellular systems studied:  cell lines Species studied:  human, mouse Comments:  P6 cells and P6 cells expressing IGF1R Enzymes shown to modify site in vitro:  Type Enzyme KINASE IGF1R (human)

Y1166-p - IGF1R (human) ▲

Modsite: DIyEtDyyRkGGkGL SwissProt Entrez-Gene Orthologous residues IGF1R (human): Y1166‑p, IGF1R (mouse): Y1168‑p, IGF1R (rat): Y1167‑p, IGF1R (pig): Y1166‑p Characterization Methods used to characterize site in vivo:  mutation of modification site, phospho-antibody, western blotting Disease tissue studied:  melanoma skin cancer Relevant cell lines - cell types - tissues:  BE (melanocyte) Cellular systems studied:  cell lines Species studied:  human, mouse Comments:  P6 cells and P6 cells expressing IGF1R Enzymes shown to modify site in vitro:  Type Enzyme KINASE IGF1R (human) Downstream Regulation Effect of modification (function):  phosphorylation Comments:  AKT phosphorylation

S473-p - Akt1 (mouse) ▲

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:  mutation of modification site, phospho-antibody, western blotting Disease tissue studied:  melanoma skin cancer Relevant cell lines - cell types - tissues:  BE (melanocyte) Cellular systems studied:  cell lines Species studied:  human, mouse Comments:  P6 cells and P6 cells expressing IGF1R Upstream Regulation Treatments, proteins and their effect on site modification:  Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes IGF-1 increase picropodophyllin IGF-1 inhibit treatment-induced increase LY294002 IGF-1 inhibit treatment-induced increase