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Previous Article | Table of Contents | Next Article 
Ligand-independent activation of c-kit receptor tyrosine kinase in a murine
mastocytoma cell line P-815 generated by a point mutation
T Tsujimura, T Furitsu, M Morimoto, K Isozaki, S Nomura, Y Matsuzawa, Y Kitamura and Y Kanakura
Department of Pathology, Osaka University Medical School, Japan.
The c-kit proto-oncogene encodes a receptor tyrosine kinase that is known
to play a crucial role in hematopoiesis, especially in mast cell growth and
differentiation. Although a number of dominant loss-of- function mutations
of c-kit gene have been well characterized in mice, rats, and humans,
little is known about the c-kit mutations contributing to
ligand-independent activation of the c-kit receptor tyrosine kinase (KIT).
In a murine mastocytoma cell line, P-815, KIT has been found to be
constitutively phosphorylated on tyrosine and activated in a
ligand-independent manner. Sequencing of the whole coding region of c-kit
cDNA showed that c-kit cDNA of P-815 cells carries a point mutation in
codon 814, resulting in amino acid substitution of Tyr for Asp. Murine
wild-type c-kit cDNA and mutant- type c-kit cDNA encoding Tyr in codon 814
were expressed in cells of a human embryonic kidney cell line, 293T. In the
transfected cells, mutant-form KITTyr814 was strikingly phosphorylated on
tyrosine and activated in immune complex kinase reaction regardless of
stimulation with a ligand for KIT (stem cell factor), whereas tyrosine
phosphorylation and activation was barely detectable in wild-form KIT. The
data presented here provide evidence for a novel activating mutation of
c-kit gene that might be involved in neoplastic growth or oncogenesis of
some cell types, including mast cells.
Volume 83,
Issue 9,
pp. 2619-2626,
05/01/1994
Copyright © 1994 by The American Society of Hematology

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