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Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs.

Hannum C., Culpepper J., Campbell D., McClanahan T., Zurawski S., Bazan J.F., Kastelein R., Hudak S., Wagner J., Mattson J., Luh J., Duda G., Martina N., Peterson D., Menon S., Shanafelt A., Muench M., Kelner G., Namikawa R., Rennick D., Roncarolo M.G., Zlotnik A., Rosnet O., Dubreuil P., Birnbaum D., Lee F., et al.

The FLT3/FLK2 receptor tyrosine kinase is closely related to two receptors, c-Kit and c-Fms, which function with their respective ligands, Kit ligand and macrophage colony-stimulating factor to control differentiation of haematopoietic and non-haematopoietic cells. FLT3/FLK2 is thought to be present on haematopoietic stem cells and found in brain, placenta and testis. We have purified to homogeneity and partially sequenced a soluble form of the FLT3/FLK2 ligand produced by mouse thymic stromal cells. We isolated several mouse and human complementary DNAs that encode polypeptides with identical N termini and different C termini. Some variants contain hydrophobic transmembrane segments, suggesting that processing may be required to release soluble ligand. The purified ligand enhances the response of mouse stem cells and a primitive human progenitor cell population to other growth factors such as interleukins IL-3 and IL-6 and to granulocyte-macrophage colony-stimulating factor, and also stimulates fetal thymocytes.

Nature 368:643-648(1994) [PubMed] [Europe PMC]

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