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Active FLT3:GRB2:p-Y-GAB2 binds PTPN11
Stable Identifier
R-HSA-9606784
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
cytosol
,
plasma membrane
ReviewStatus
5/5
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Immune System (Homo sapiens)
Cytokine Signaling in Immune system (Homo sapiens)
FLT3 Signaling (Homo sapiens)
Active FLT3:GRB2:p-Y-GAB2 binds PTPN11 (Homo sapiens)
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Feline McDonough Sarcoma-like tyrosine kinase (FLT3) is a member of the class III tyrosine kinase receptor family. Ligand binding induces conformational changes in the FLT3 receptor, which facilitates its dimerization and autophosphorylation. Once fully active, FLT3 receptors can associate with growth factor receptor-bound protein 2 (GRB2), which then recruits GRB2-associated-binding protein 2 (GAB2). Consequently, GAB2 is phosphorylated and recruits tyrosine-protein phosphatase non-receptor type 11 (PTPN11). The serine residue at position 623 in GAB2 is known to be involved in PTPN11 binding (Zhang et al. 2000, Arnaud et al. 2004). The precise association mechanism of GAB2 and PTPN11 is unclear. Experiments confirming this event were performed in mouse cells. Interaction of FLT3 with PTPN11 is known to trigger STAT5 activation in various pathological conditions.
Literature References
PubMed ID
Title
Journal
Year
11027663
Flt3 ligand induces tyrosine phosphorylation of gab1 and gab2 and their association with shp-2, grb2, and PI3 kinase
Zhang, S
,
Broxmeyer, HE
Biochem. Biophys. Res. Commun.
2000
15356145
Phosphorylation of Grb2-associated binder 2 on serine 623 by ERK MAPK regulates its association with the phosphatase SHP-2 and decreases STAT5 activation
Bertoglio, J
,
Arnaud, M
,
Deon, C
,
Loyaux, D
,
Crouin, C
J. Immunol.
2004
Participants
Input
Active FLT3:GRB2:p-Y-GAB2 [plasma membrane]
(Homo sapiens)
PTPN11 [cytosol]
(Homo sapiens)
Output
Active FLT3:GRB2:p-Y-GAB2:PTPN11 [plasma membrane]
(Homo sapiens)
Participates
as an event of
FLT3 Signaling (Homo sapiens)
Inferred From
Active Flt3:Grb2:p-Y-Gab2 binds Ptpn11 (Mus musculus)
Authored
Varusai, TM (2019-01-14)
Reviewed
Traer, E (2019-05-03)
Joshi, S (2019-05-21)
Created
Varusai, TM (2018-04-25)
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