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

C. Hannum, J. Culpepper, D. Campbell, T. McClanahan, S. Zurawski, R. Kastelein, J. F. Bazan, S. Hudak, J. Wagner, J. Mattson, J. Luh, G. Duda, N. Martina, D. Peterson, S. Menon, A. Shanafelt, M. Muench, G. Kelner, R. Namikawa, D. Rennick & 6 others M. G. Roncarolo, A. Zlotnik, O. Rosnet, P. Dubreuil, D. Birnbaum, F. Lee

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Abstract

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 polypeptides with identical N termini and different C termini. Some variants contain hydrophobic transmembrane segments, suggesting that processing may be required to release soluble lig-and. 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.

Original languageEnglish
Pages (from-to)643-648
Number of pages6
JournalNature
Volume368
Issue number6472
Publication statusPublished - 1994

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Receptor Protein-Tyrosine Kinases
Hematopoietic Stem Cells
Interleukin-3
RNA
Ligands
Stem Cells
Growth
Proto-Oncogene Proteins c-kit
Stem Cell Factor
Macrophage Colony-Stimulating Factor
Thymocytes
Granulocyte-Macrophage Colony-Stimulating Factor
Stromal Cells
Placenta
Interleukin-6
Intercellular Signaling Peptides and Proteins
Complementary DNA
Peptides
Brain
Population

ASJC Scopus subject areas

  • General

Cite this

Hannum, C., Culpepper, J., Campbell, D., McClanahan, T., Zurawski, S., Kastelein, R., ... Lee, F. (1994). Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs. Nature, 368(6472), 643-648.

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.; Kastelein, R.; Bazan, J. F.; 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.

In: Nature, Vol. 368, No. 6472, 1994, p. 643-648.

Research output: Contribution to journalArticle

Hannum, C, Culpepper, J, Campbell, D, McClanahan, T, Zurawski, S, Kastelein, R, Bazan, JF, 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, MG, Zlotnik, A, Rosnet, O, Dubreuil, P, Birnbaum, D & Lee, F 1994, 'Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs', Nature, vol. 368, no. 6472, pp. 643-648.
Hannum C, Culpepper J, Campbell D, McClanahan T, Zurawski S, Kastelein R et al. Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs. Nature. 1994;368(6472):643-648.
Hannum, C. ; Culpepper, J. ; Campbell, D. ; McClanahan, T. ; Zurawski, S. ; Kastelein, R. ; Bazan, J. F. ; 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. / Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs. In: Nature. 1994 ; Vol. 368, No. 6472. pp. 643-648.
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abstract = "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 polypeptides with identical N termini and different C termini. Some variants contain hydrophobic transmembrane segments, suggesting that processing may be required to release soluble lig-and. 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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AU - Hannum, C.

AU - Culpepper, J.

AU - Campbell, D.

AU - McClanahan, T.

AU - Zurawski, S.

AU - Kastelein, R.

AU - Bazan, J. F.

AU - Hudak, S.

AU - Wagner, J.

AU - Mattson, J.

AU - Luh, J.

AU - Duda, G.

AU - Martina, N.

AU - Peterson, D.

AU - Menon, S.

AU - Shanafelt, A.

AU - Muench, M.

AU - Kelner, G.

AU - Namikawa, R.

AU - Rennick, D.

AU - Roncarolo, M. G.

AU - Zlotnik, A.

AU - Rosnet, O.

AU - Dubreuil, P.

AU - Birnbaum, D.

AU - Lee, F.

PY - 1994

Y1 - 1994

N2 - 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 polypeptides with identical N termini and different C termini. Some variants contain hydrophobic transmembrane segments, suggesting that processing may be required to release soluble lig-and. 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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