Rocnik JL, et al. (2006) Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by FLT3-ITD. Blood 108, 1339-45 16627759

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Y589-p - FLT3 (human) ▲

Modsite: TGSSDNEyFyVDFRE SwissProt Entrez-Gene Orthologous residues FLT3 (human): Y589‑p, FLT3 (mouse): Y590‑p Characterization Methods used to characterize site in vivo:  mutation of modification site Relevant cell lines - cell types - tissues:  32D (myeloid) [FLT3 (human)], BaF3 ('B lymphocyte, precursor') [FLT3 (human)] Cellular systems studied:  cell lines Species studied:  mouse Comments:  FLT3 is either WT or consitutively active due to internal tandem duplications (ITD) as observed in AML cells. With and without point mutations. Downstream Regulation Effect of modification (function):  phosphorylation Effect of modification (process):  cell growth, altered Comments:  The double mutation Y589/591F has a slower growth rate (this is in the ligand-independent, constitutive active allele)., While none of the single mutations affected STAT-5 phosphotyrosine levels, 3 double mutations did: Y591/726F, Y591/955F, Y589/591F (all three pairs have Y591F in common).

Y591-p - FLT3 (human) ▲

Modsite: SSDNEyFyVDFREyE SwissProt Entrez-Gene Orthologous residues FLT3 (human): Y591‑p, FLT3 (mouse): Y592‑p Characterization Methods used to characterize site in vivo:  mutation of modification site Relevant cell lines - cell types - tissues:  32D (myeloid) [FLT3 (human)], BaF3 ('B lymphocyte, precursor') [FLT3 (human)] Cellular systems studied:  cell lines Species studied:  mouse Comments:  FLT3 is either WT or consitutively active due to internal tandem duplications (ITD) as observed in AML cells. With and without point mutations. Enzymes shown to modify site in vitro:  Type Enzyme KINASE FLT3 (human) Downstream Regulation Effect of modification (function):  phosphorylation Effect of modification (process):  cell growth, altered Comments:  The double mutation Y589/591F has a slower growth rate (this is in the ligand-independent, constitutive active allele)., While none of the single mutations affected STAT-5 phosphotyrosine levels, 3 double mutations did: Y591/726F, Y591/955F, Y589/591F (all three pairs have Y591F in common).

Y726-p - FLT3 (human) ▲

Modsite: kEHNFSFyPtFQSHP SwissProt Entrez-Gene Orthologous residues FLT3 (human): Y726‑p, FLT3 (mouse): Y727‑p Characterization Methods used to characterize site in vivo:  mutation of modification site Relevant cell lines - cell types - tissues:  32D (myeloid) [FLT3 (human)], BaF3 ('B lymphocyte, precursor') [FLT3 (human)] Cellular systems studied:  cell lines Species studied:  mouse Comments:  FLT3 is either WT or consitutively active due to internal tandem duplications (ITD) as observed in AML cells. With and without point mutations. Enzymes shown to modify site in vitro:  Type Enzyme KINASE FLT3 (human) Downstream Regulation Effect of modification (function):  phosphorylation Comments:  While none of the single mutations affected STAT-5 phosphotyrosine levels, 3 double mutations did: Y591/726F, Y591/955F, Y589/591F (all three pairs have Y591F in common).

Y842-p - FLT3 (human) ▲
Modsite: DIMSDsNyVVRGNAR SwissProt Entrez-Gene Orthologous residues FLT3 (human): Y842‑p, FLT3 (mouse): Y845‑p Characterization Enzymes shown to modify site in vitro:  Type Enzyme KINASE FLT3 (human)

Y955-p - FLT3 (human) ▲

Modsite: ADAEEAMyQNVDGRV SwissProt Entrez-Gene Orthologous residues FLT3 (human): Y955‑p, FLT3 (mouse): Y958‑p Characterization Methods used to characterize site in vivo:  mutation of modification site Relevant cell lines - cell types - tissues:  32D (myeloid) [FLT3 (human)], BaF3 ('B lymphocyte, precursor') [FLT3 (human)] Cellular systems studied:  cell lines Species studied:  mouse Comments:  FLT3 is either WT or consitutively active due to internal tandem duplications (ITD) as observed in AML cells. With and without point mutations. Enzymes shown to modify site in vitro:  Type Enzyme KINASE FLT3 (human) Downstream Regulation Effect of modification (function):  phosphorylation Comments:  While none of the single mutations affected STAT-5 phosphotyrosine levels, 3 double mutations did: Y591/726F, Y591/955F, Y589/591F (all three pairs have Y591F in common).

Y969-p - FLT3 (human) ▲

Modsite: VSECPHtyQNrrPFS SwissProt Entrez-Gene Orthologous residues FLT3 (human): Y969‑p, FLT3 (mouse): Y972‑p Characterization Methods used to characterize site in vivo:  mutation of modification site Relevant cell lines - cell types - tissues:  32D (myeloid) [FLT3 (human)], BaF3 ('B lymphocyte, precursor') [FLT3 (human)] Cellular systems studied:  cell lines Species studied:  mouse Comments:  FLT3 is either WT or consitutively active due to internal tandem duplications (ITD) as observed in AML cells. With and without point mutations. Enzymes shown to modify site in vitro:  Type Enzyme KINASE FLT3 (human)

T203-p - ERK1 (mouse) ▲

Modsite: HDHtGFLtEyVAtRW SwissProt Entrez-Gene Orthologous residues ERK1 (human): T202‑p, ERK1 iso2 (human): T202‑p, ERK1 iso3 (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 Relevant cell lines - cell types - tissues:  BaF3 ('B lymphocyte, precursor') [FLT3 (human)] Cellular systems studied:  cell lines Species studied:  mouse Upstream Regulation Treatments, proteins and their effect on site modification:  Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes FL increase in WT FLT3 receptor (lost in multiple Y->F allele)

Y205-p - ERK1 (mouse) ▲

Modsite: HtGFLtEyVAtRWyR SwissProt Entrez-Gene Orthologous residues ERK1 (human): Y204‑p, ERK1 iso2 (human): Y204‑p, ERK1 iso3 (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 Relevant cell lines - cell types - tissues:  BaF3 ('B lymphocyte, precursor') [FLT3 (human)] Cellular systems studied:  cell lines Species studied:  mouse Upstream Regulation Treatments, proteins and their effect on site modification:  Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes FL increase in WT FLT3 receptor (lost in multiple Y->F allele)

T183-p - ERK2 (mouse) ▲

Modsite: HDHtGFLtEyVAtRW SwissProt Entrez-Gene Orthologous residues ERK2 (human): T185‑p, ERK2 (mouse): T183‑p, ERK2 (rat): T183‑p, ERK2 (chicken): T193‑p, ERK2 (cow): T185‑p Characterization Methods used to characterize site in vivo:  phospho-antibody, western blotting Relevant cell lines - cell types - tissues:  BaF3 ('B lymphocyte, precursor') [FLT3 (human)] Cellular systems studied:  cell lines Species studied:  mouse Upstream Regulation Treatments, proteins and their effect on site modification:  Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes FL increase in WT FLT3 receptor (lost in multiple Y->F allele)

Y185-p - ERK2 (mouse) ▲

Modsite: HtGFLtEyVAtRWYR SwissProt Entrez-Gene Orthologous residues ERK2 (human): Y187‑p, ERK2 (mouse): Y185‑p, ERK2 (rat): Y185‑p, ERK2 (chicken): Y195‑p, ERK2 (cow): Y187‑p Characterization Methods used to characterize site in vivo:  phospho-antibody, western blotting Relevant cell lines - cell types - tissues:  BaF3 ('B lymphocyte, precursor') [FLT3 (human)] Cellular systems studied:  cell lines Species studied:  mouse Upstream Regulation Treatments, proteins and their effect on site modification:  Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes FL increase in WT FLT3 receptor (lost in multiple Y->F allele)