Reactome | Phosphorylation of STAT5 by cytosolic FGFR1 fusions

Phosphorylation of STAT5 by cytosolic FGFR1 fusions

Stable Identifier

R-HSA-1839112

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

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Disease (Homo sapiens)

- Diseases of signal transduction by growth factor receptors and second messengers (Homo sapiens)
  - Signaling by FGFR in disease (Homo sapiens)
    - Signaling by FGFR1 in disease (Homo sapiens)
      - FGFR1 mutant receptor activation (Homo sapiens)
        
        Signaling by cytosolic FGFR1 fusion mutants (Homo sapiens)
        
        Phosphorylation of STAT5 by cytosolic FGFR1 fusions (Homo sapiens)

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Phosphorylation of STAT5 by cytosolic FGFR1 fusions

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Activation of a subset of FGFR1-fusions (ZMYM2, BCR, FGFR1OP2 and CUX) has been shown to result in downstream phosphorylation of STAT5 proteins at Y694. This phosphorylation is dependent on the FGFR1 fusion, as the STAT5 phosphorylation is abrogated in the presence of an FGFR1-kinase dead fusion (Heath and Cross, 2004; Smedley, 1999; Chase, 2007; Wasage, 2011).

Literature References

PubMed ID	Title	Journal	Year
10935490	ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5 Abdul-Rauf, M, Demiroglu, A, Smedley, D, Cross, NC, Heath, C, Cooper, C, Shipley, J	Neoplasia	1999
14660670	Critical role of STAT5 activation in transformation mediated by ZNF198-FGFR1 Cross, NC, Heath, C	J Biol Chem	2004
17698633	Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome Grand, FH, Cross, NC, Chase, A	Blood	2007
21330321	The kinase inhibitor TKI258 is active against the novel CUX1-FGFR1 fusion detected in a patient with T-lymphoblastic leukemia/lymphoma and t(7;8)(q22;p11) Wasag, B, Vandenberghe, P, Meeus, P, Lierman, E, Cools, J	Haematologica	2011

Participants

Input

Output

Participates

as an event of

Signaling by cytosolic FGFR1 fusion mutants (Homo sapiens)

Catalyst Activity

protein tyrosine kinase activity of cytosolic p-FGFR1 fusion mutant dimers [cytosol]

Physical Entity

cytosolic p-FGFR1 fusion mutant dimers [cytosol] (Homo sapiens)

Activity

protein tyrosine kinase activity (GO:0004713)

Functional status

Gain of function of cytosolic p-FGFR1 fusion mutant dimers [cytosol]

Disease Entity

Status

gain of function via gene fusion

Disease

Name	Identifier	Synonyms
subacute leukemia	DOID:3264
myelodysplastic myeloproliferative cancer	DOID:4972	Myeloproliferative/Myelodysplastic syndromes, unclassifiable myelodysplastic myeloproliferative disease, Unclassifiable Myeloproliferative/Myelodysplastic syndrome, Myelodysplastic/myeloproliferative disease (morphologic abnormality)
acute lymphocytic leukemia	DOID:9952
cancer	DOID:162	malignant tumor, malignant neoplasm, primary cancer

Authored

Rothfels, K (2012-02-10)

Reviewed

Ezzat, S (2012-05-15)

Created

Rothfels, K (2011-10-27)