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PubMed Id: 16627759 
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
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.
Information from this record has been curated, but not yet edited in PhosphoSitePlus® and may be incomplete.
Click on the protein name to open the protein page, and on the RSD number to open the site page.
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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

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
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
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)


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