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Identification and characterization of a soluble c-kit receptor produced by human hematopoietic cell lines
- Source :
- Blood. 85(8)
- Publication Year :
- 1995
-
Abstract
- 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.
- Subjects :
- Stem Cell Factor
Base Sequence
Molecular Sequence Data
Receptor Protein-Tyrosine Kinases
Hematopoietic Cell Growth Factors
Hematopoietic Stem Cells
Binding, Competitive
Burkitt Lymphoma
Recombinant Proteins
Neoplasm Proteins
Molecular Weight
Proto-Oncogene Proteins c-kit
Solubility
Leukemia, Megakaryoblastic, Acute
Proto-Oncogene Proteins
Receptors, Colony-Stimulating Factor
Neoplastic Stem Cells
Tumor Cells, Cultured
Humans
Amino Acid Sequence
Leukemia, Erythroblastic, Acute
Protein Binding
Subjects
Details
- ISSN :
- 00064971
- Volume :
- 85
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.pmid..........ebfafb464368ecf2ab68ce3d2858b562