Novel murine myeloid cell lines that exhibit a differentiation switch in response to IL-3 or GM-CSF, or to different constitutively active mutants of the CM-CSF receptor beta subunit

McCormack, Matthew P. and Gonda, Thomas J. (2000) Novel murine myeloid cell lines that exhibit a differentiation switch in response to IL-3 or GM-CSF, or to different constitutively active mutants of the CM-CSF receptor beta subunit. Blood, 95 1: 120-127.

Author McCormack, Matthew P.
Gonda, Thomas J.
Title Novel murine myeloid cell lines that exhibit a differentiation switch in response to IL-3 or GM-CSF, or to different constitutively active mutants of the CM-CSF receptor beta subunit
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
1528-0020
Publication date 2000-01
Sub-type Article (original research)
Volume 95
Issue 1
Start page 120
End page 127
Total pages 8
Place of publication Washington, DC, Unite States
Publisher American Society of Hematology
Language eng
Abstract Several activating mutations have recently been described in the common beta subunit for the human interleukin(IL)-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors (h beta c), Two of these, FI Delta and 1374N, result, respectively, in a 37-amino acid duplication and an isoleucine-to-asparagine substitution in the extracellular domain. A third, V449E, leads to valine-to-glutamic acid substitution in the transmembrane domain. Previous studies have shown that when expressed in murine hemopoietic cells in vitro, the extracellular mutants can confer factor independence on only the granulocyte-macrophage lineage while the transmembrane mutant can do so to all cell types of the myeloid and erythroid compartments. To further study the signaling properties of the constitutively active hpc mutants, we have used novel murine hemopoietic cell lines, which we describe in this report. These lines, FDB1 and FDB2, proliferate in murine IL-3 and undergo granulocyte-macrophage differentiation in response to murine GM-CSF, We find that while the transmembrane mutant, V449E, confers factor-independent proliferation on these cell lines, the extracellular hpc mutants promote differentiation. Hence, in addition to their ability to confer factor independence on distinct cell types, transmembrane and extracellular activated h beta c mutants deliver distinct signals to the same cell type. Thus, the FDB cell lines, in combination with activated h beta c mutants, constitute a powerful new system to distinguish between signals that determine hemopoietic proliferation or differentiation. (C) 2000 by The American Society of Hematology.
Keyword Hematology
Colony-stimulating Factor
Interleukin-3 Il-3
Alpha-chain
Erythroid-differentiation
Point Mutation
Neu Oncogene
Map Kinase
Activation
Reconstitution
Proliferation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Mon, 13 Aug 2007, 11:31:51 EST