Oncostatin M and Leukemia Inhibitory Factor Do Not Use the Same Functional Receptor in Mice

作者: Masatoshi Ichihara , Takahiko Hara , Heejung Kim , Takashi Murate , Atsushi Miyajima

DOI: 10.1182/BLOOD.V90.1.165

关键词:

摘要: Oncostatin M (OSM) and leukemia inhibitory factor (LIF ) are members of the interleukin-6 (IL-6) subfamily cytokines that use a common signal transducer gp130. Human OSM (hOSM) LIF share functional high-affinity receptor is composed gp130 β subunit (LIFRβ). A second for hOSM was recently found to be formed by subunit. However, nature murine (mOSM) its receptors has remained unknown. Using cloned mOSM cDNA, we produced recombinant studied biological activity structure. Murine hematopoietic cell lines M1 DA1.a, an embryonic stem line CCE, Ba/F3 transfectants expressing LIFRβ responded (mLIF equally well, while these cells only at 30-fold 100-fold higher concentration than those mLIF hOSM. In contrast, NIH3T3 mOSM, but not Scatchard plot analyses showed bound with low-affinity (kd = 2.8 4.2 nmol/L) binding affinity did increase in presence LIFRβ. 660 pmol/L), whereas bind all. These results indicate unlike hOSM, do same receptor, delivers signals through specific complex. Further studies mice will define physiological roles OSM.

参考文章(40)
David P. Gearing, The leukemia inhibitory factor and its receptor. Advances in Immunology. ,vol. 53, pp. 31- 58 ,(1993) , 10.1016/S0065-2776(08)60497-6
M.M. Shen, R.C. Skoda, R.D. Cardiff, J. Campos-Torres, P. Leder, D.M. Ornitz, Expression of LIF in transgenic mice results in altered thymic epithelium and apparent interconversion of thymic and lymph node morphologies. The EMBO Journal. ,vol. 13, pp. 1375- 1385 ,(1994) , 10.1002/J.1460-2075.1994.TB06391.X
Peter J. Munson, [41] LIGAND: A computerized analysis of ligand binding data Methods in Enzymology. ,vol. 92, pp. 543- 576 ,(1983) , 10.1016/0076-6879(83)92044-X
I H Hoggatt, A G Bruce, T M Rose, Oncostatin M is a differentiation factor for myeloid leukemia cells. Journal of Immunology. ,vol. 149, pp. 1271- 1275 ,(1992)
J Gauldie, C D Richards, H Baumann, T J Brown, M Shoyab, Recombinant oncostatin M stimulates the production of acute phase proteins in HepG2 cells and rat primary hepatocytes in vitro. Journal of Immunology. ,vol. 148, pp. 1731- 1736 ,(1992)
J Gauldie, C D Richards, T J Brown, M Shoyab, Selective regulation of metalloproteinase inhibitor (TIMP-1) by oncostatin M in fibroblasts in culture. Journal of Immunology. ,vol. 150, pp. 5596- 5603 ,(1993)
A. Yoshimura, M. Ichihara, I. Kinjyo, M. Moriyama, N. G. Copeland, D. J. Gilbert, N. A. Jenkins, T. Hara, A. Miyajima, Mouse oncostatin M: an immediate early gene induced by multiple cytokines through the JAK-STAT5 pathway. The EMBO Journal. ,vol. 15, pp. 1055- 1063 ,(1996) , 10.1002/J.1460-2075.1996.TB00443.X
J Liu, B Modrell, A Aruffo, J.S. Marken, T Taga, K Yasukawa, M Murakami, T Kishimoto, M Shoyab, Interleukin-6 signal transducer gp130 mediates oncostatin M signaling. Journal of Biological Chemistry. ,vol. 267, pp. 16763- 16766 ,(1992) , 10.1016/S0021-9258(18)41845-5
Kazuo Sugamura, Hironobu Asao, Motonari Kondo, Nobuyuki Tanaka, Naoto Ishii, Masataka Nakamura, Toshikazu Takeshita, The Common γ-Chain for Multiple Cytokine Receptors Advances in Immunology. ,vol. 59, pp. 225- 277 ,(1995) , 10.1016/S0065-2776(08)60632-X