LIGAND FOR FLT3 FLK2 RECEPTOR TYROSINE KINASE REGULATES GROWTH OF HEMATOPOIETIC STEM-CELLS AND IS ENCODED BY VARIANT RNAS

THE FLT3/FLK2 receptor tyrosine kinase is closely related to two recep tors, c-Kit and c-Fms, which function with their respective ligands, K it ligand and macrophage colony-stimulating factor to control differen tiation of haematopoietic and non-haematopoietic cells1-5. FLT3/FLK2 i s thought to be present on haematopoietic stem cells and found in brai n, placenta and testis3-5. We have purified to homogeneity and partial ly sequenced a soluble form of the FLT3/FLK2 ligand produced by mouse thymic stromal cells. We isolated several mouse and human complementar y DNAs that encode polypeptide with identical N termini and different C termini. Some variants contain hydrophobic transmembrane segments, s uggesting that processing may be required to release soluble ligand. T he purified ligand enhances the response of mouse stem cells and a pri mitive human progenitor cell population to other growth factors such a s interleukins IL-3 and IL-6 and to granulocyte-macrophage colony-stim ulating factor, and also stimulates fetal thymocytes.