The tyrosine kinase FES is an essential effector of KITD816V proliferation signal.
Blood
; 110(7): 2593-9, 2007 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-17595334
ABSTRACT
KIT is a tyrosine kinase receptor that is aberrantly activated in several neoplasms. In human pathologies, the most frequent mutation of KIT occurs at codon 816. The resulting KIT mutant protein is activated in the absence of ligand and is resistant to the clinically available inhibitors of KIT. In this report, we provide evidence for an essential function of the cytoplasmic tyrosine kinase FES downstream of KIT(D816V). FES is phosphorylated on tyrosine residues in cells that carry KIT(D816V) mutation, and this phosphorylation is KIT dependent. Reduction of FES expression using RNA interference results in decreased cell proliferation in human or murine cells harboring KIT(D816V) or the homologous mouse mutation KIT(D814Y). The reduced cell growth can be rescued using another cytokine (granulocyte-macrophage colony-stimulating factor [GM-CSF]) and is not observed when the closely related fer gene is targeted. Finally, signaling downstream of KIT(D816V) is altered in cells lacking FES expression. This study shows a major function of FES downstream of activated KIT receptor and thereby points to FES as a novel target in KIT-related pathologies.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Aspartic Acid
/
Proto-Oncogene Proteins c-kit
/
Proto-Oncogene Proteins c-fes
Limits:
Animals
/
Humans
Language:
En
Journal:
Blood
Year:
2007
Document type:
Article
Affiliation country: