TEL-Syk fusion constitutively activates PI3-K/Akt, MAPK and JAK2-independent STAT5 signal pathways.
Leukemia
; 18(3): 548-55, 2004 Mar.
Article
in En
| MEDLINE
| ID: mdl-14749700
ABSTRACT
We previously reported the fusion of the TEL gene to the Syk gene in myelodysplastic syndrome with t(9;12)(q22;p12). TEL-Syk fusion transformed interleukin-3 (IL-3)-dependent murine hematopoietic cell line BaF3 to growth factor independence. Here, we investigate the intracellular signal transduction of the stable transfectants. TEL-Syk fusion protein was associated with the p85 subunit of phosphatidyl inositol 3 kinase (PI3-K) followed by the activation of Akt in the absence of IL-3. Vav, phospholipase C-gamma2 and mitogen-activated protein kinase (MAPK) were also constitutively activated. TEL-Syk also activated the signal transducer and activator of transcription 5 (STAT5) in the absence of Janus kinase 2 activation. None of these kinases were phosphorylated in the BaF3 cells transfected with TELDeltaPNT-Syk in which the oligomerization domain of TEL was deleted. Inhibitor analysis showed that the MAPK pathway was important in TEL-Syk-mediated cell proliferation. The immunofluorescence technique revealed that the TEL-Syk fusion protein was located in the cytoplasm. These data suggest that TEL-Syk fusion protein in the cytoplasm leads to the constitutive activation of PI3-K/Akt, MAPK and STAT5 signal pathways, which are closely involved in IL-3-independent cell proliferation of BaF3 cells.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Repressor Proteins
/
Protein-Tyrosine Kinases
/
Signal Transduction
/
Trans-Activators
/
Proto-Oncogene Proteins
/
Protein Serine-Threonine Kinases
/
Phosphatidylinositol 3-Kinases
/
DNA-Binding Proteins
/
Enzyme Precursors
/
Milk Proteins
Limits:
Humans
Language:
En
Journal:
Leukemia
Journal subject:
HEMATOLOGIA
/
NEOPLASIAS
Year:
2004
Document type:
Article
Affiliation country:
Japan
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM