Receptor functions and ligand-dependent transforming potential of a chimeric kit proto-oncogene.
The c-kit proto-oncogene, the cellular homolog of the transforming gene of a feline retrovirus, encodes a transmembrane tyrosine kinase homologous to receptors for growth factors. To study the cellular function of c-kit, we constructed a chimeric molecule composed of the extracellular portion of the receptor for epidermal growth factor (EGF) and the transmembrane and cytoplasmic domains of p145kit. The hybrid molecule was properly expressed in murine fibroblasts and displayed specific binding of EGF (Kd, 3 x 10(-8) M). Activation of the chimeric receptor by EGF stimulated the tyrosine kinase activity of kit and led to the generation of a potent mitogenic signal. Moreover, cells expressing the chimeric receptor acquired a transformed phenotype once they were stimulated with the heterologous ligand.
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
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Lev
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Yarden
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Givol
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002678:Chimera; D004261:DNA Replication; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit; D011519:Proto-Oncogenes; D014162:Transfection
D008024:Ligands; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit