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

被引:407
作者
HANNUM, C [1 ]
CULPEPPER, J [1 ]
CAMPBELL, D [1 ]
MCCLANAHAN, T [1 ]
ZURAWSKI, S [1 ]
BAZAN, JF [1 ]
KASTELEIN, R [1 ]
HUDAK, S [1 ]
WAGNER, J [1 ]
MATTSON, J [1 ]
LUH, J [1 ]
DUDA, G [1 ]
MARTINA, N [1 ]
PETERSON, D [1 ]
MENON, S [1 ]
SHANAFELT, A [1 ]
MUENCH, M [1 ]
KELNER, G [1 ]
NAMIKAWA, R [1 ]
RENNICK, D [1 ]
RONCAROLO, MG [1 ]
ZLOTNIK, A [1 ]
ROSNET, O [1 ]
DUBREUIL, P [1 ]
BIRNBAUM, D [1 ]
LEE, F [1 ]
机构
[1] INSERM, U119, F-13009 MARSEILLE, FRANCE
关键词
D O I
10.1038/368643a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 cells1-5. FLT3/FLK2 is thought to be present on haematopoietic stem cells and found in brain, placenta and testis3-5. 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 polypeptide 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.
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页码:643 / 648
页数:6
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