p-BCR-pFGFR1 binds GRB2:GAB2

Stable Identifier
R-HSA-1839095
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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p-BCR-pFGFR1 binds GRB2:GAB2
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Proliferation of BCR-FGFR1 fusion proteins is blocked by treatment with the PI3K inhibitor LY294002, suggesting the activation of this pathway downstream of BCR-FGFR1 phosphorylation. Y177 has been shown to be a binding site for GRB2 and to be required for the both the phosphorylation of GAB2 and the development of CML-like disease (Roumiantsev, 2004, Demiroglu, 2001). By analogy with studies in BCR-ABL, where mutation of Y177 abrogates recruitment of PI3K activity to the fusion protein (Sattler, 2002), this suggests that Y177 may serve as a docking site for a complex of GRB2:GAB1:PI3K in the context of BCR-FGFR1 as well.
Literature References
PubMed ID Title Journal Year
11739186 The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins

Doody, ML, Demiroglu, A, Carnicero, F, Brody, JP, Melo, JV, Koduru, P, Cross, NC, Heath, C, Hawson, G, Taylor, K, Steer, EJ, Goldman, JM, Reiter, A, Rodwell, R, Bentley, M, Allen, SL

Blood 2001
15050920 Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations

Krause, DS, Dimitri, CA, Asiedu, F, Van Etten, RA, Cross, NC, Roumiantsev, S, Neumann, CA

Cancer Cell 2004
12124177 Critical role for Gab2 in transformation by BCR/ABL

Iwasaki, H, Gesbert, F, Li, S, Neel, BG, Gu, H, Podar, K, Malouf, NA, Pride, YB, Van Etten, RA, Quinnan, LR, Sattler, M, Mohi, MG, Griffin, JD

Cancer Cell 2002
Participants
Input
Output
Participates
as an event of
Functional status

Gain of function of pY177-BCR-p-FGFR1 fusion mutant dimer [cytosol]

Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
chronic myeloid leukemia DOID:8552 CML, chronic myelogenous leukemia, no ICD-O subtype (morphologic abnormality), chronic myeloid leukemia, disease (disorder), chronic myeloid leukemia without mention of remission, CML - chronic Myelogenous Leukemia, chronic myeloid leukemia in remission (disorder), Myeloid Leukemia, chronic, CML in Remission, chronic myeloid leukemia in remission, chronic myeloid leukaemia, chronic myeloid leukemia NOS (disorder)
Authored
Rothfels, K  (2012-02-10)
Reviewed
Ezzat, S  (2012-05-15)
Created
Rothfels, K  (2011-10-27)
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