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Identification and characterization of a soluble c-kit receptor produced by
human hematopoietic cell lines
AM Turner, LG Bennett, NL Lin, J Wypych, TD Bartley, RW Hunt, HL Atkins, KE Langley, V Parker and F Martin
Division of Hematology, University of Washington, Seattle 98195, USA.
Stem cell factor (SCF) triggers cell growth by binding to cell surface
c-kit receptors. Soluble forms of several cytokine receptors have been
described and may play a role in the modulation of cytokine activity in
vivo. For these reasons, we investigated whether human hematopoietic cells
produce soluble c-kit receptors. The human leukemia cell lines OCIM1 and
MO7e display approximately 80,000 and approximately 35,000 high-affinity
cell surface c-kit receptors, respectively. Soluble c-kit receptors were
detected by enzyme immunoassay in OCIM1 and MO7e culture supernatants. We
determined the molecular weight and binding affinity of soluble c-kit
receptor produced by OCIM1 cells, soluble c-kit receptor purified from
human serum, and recombinant soluble c-kit receptor expressed in CHO cells.
The three soluble c-kit receptors each have a molecular weight of 98 kD.
Quantitative binding experiments with 125I-SCF indicate that the soluble
c-kit receptors obtained from human serum or OCIM1 cells have binding
affinities for SCF of approximately 200 to 300 pmol/L, in contrast to the
recombinant form, which has a binding affinity of approximately 1.5 nmol/L.
All three forms of the soluble c-kit receptor were able to compete with
c-kit receptors on OCIM1 cells for 125I-SCF binding. Thus human
hematopoietic cells can produce a soluble form of the c-kit receptor that
retains high-affinity SCF binding activity. We speculate that the soluble
c-kit receptor may bind SCF and function as a receptor antagonist in vivo.
Volume 85,
Issue 8,
pp. 2052-2058,
04/15/1995
Copyright © 1995 by The American Society of Hematology

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