The box-1 region of the leukemia inhibitory factor receptor alpha-chain cytoplasmic domain is sufficient for hemopoietic cell proliferation and differentiation
- Author(s)
- Zhang, Y; Willson, T; Metcalf, D; Cary, D; Hilton, DJ; Clark, R; Nicola, NA;
- Details
- Publication Year 1998-12-18,Volume 273,Issue #51,Page 34370-34383
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Publication Type
- Journal Article
- Abstract
- Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that acts on a variety of cell types and regulates cell proliferation and differentiation. The functional receptor for LIF is composed of LIFR alpha-chain (LIFR alpha) and gp130 both of which are shared in the functional receptors for oncostatin M, ciliary neurotrophic factor, and cardiotrophin-1. By using stable transfection of wildtype or cytoplasmic deletion mutants of LIFR alpha together with full-length gp130 into Ba/F3 cells, we found that cells expressing gp130 and an extensively deleted mutant LIFR alpha containing only the box-1 region were capable of proliferating in response to LIF, although LIF-dependent long term growth of these cells was seriously impaired. Using a similar strategy to generate WEHI-3BD+ cells expressing gp130 and wild-type or truncation mutants of LIFR alpha, studies revealed that the box-1 region of the LIFR alpha was also sufficient for LIF-dependent induction of different aspects of differentiation, including up-regulation of macrophage surface marker expression, morphological change, and cell migration in agar culture. However, the C-terminal region of the LIFR alpha although not essential for intracellular signaling, was important for efficient receptor-mediated ligand internalization. In summary, the membrane-proximal box-1 region plays a dominant role in LIF-induced signal transduction of both proliferation and differentiation.
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- COLONY-STIMULATING FACTOR; IL-6 SIGNAL TRANSDUCER; CILIARY NEUROTROPHIC FACTOR; GROWTH-FACTOR RECEPTOR; ONCOSTATIN-M RECEPTOR; C-KIT RECEPTOR; HEMATOPOIETIC-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; MONOCLONAL-ANTIBODY; STAT3 ACTIVATION
- Publisher's Version
- https://doi.org/10.1074/jbc.273.51.34370
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- Refer to copyright notice on published article.
Creation Date: 1998-12-18 12:00:00