Leukemia inhibitory factor development

Thrombopoiesis is the term used to describe the process of platelet production. The bone marrow manufactures 40,000 platelets/mL of blood each day. Proliferation and differentiation of platelet precursors are thought to be primarily influenced by cytokines such as IL-6, IL-11, leukemia inhibitory factor, and perhaps most specifically, by thrombopoietin (TPO or megakaryocyte growth and development factor see Fig. 98-6). Other hematopoietins that may act in concert, producing synergistic effects include IL-3, IL-1, GM-CSF, EPO, and Scf.34 The platelet survival time is a clinical test that can estimate the rate of platelet turnover. In healthy individuals, this time is 9.5 0.6 days.36... 

Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death. Development 121 (5), 1283-1299. 

Murphy, M., Reid, K., Brown, M.A. and Bartlett, P.F. (1993) Involvement of leukemia inhibitory factor and nerve growth factor in the development of dorsal root ganglion neurons. Development 111 1173-1182... 

Kotzbauer, P.T., Lampe, P.A., Estus, S., Milbrandt, J. and Johnson, E.M. (1994) Postnatal development of survival responsiveness in rat sympathetic neurons to leukemia inhibitory factor and ciliary neurotrophic factor. Neuron 12 763-773. 

Mayer, M., Bhakoo, K. and Noble, M. (1994) Ciliary neurotrophic factor and leukemia inhibitory factor promote the generation, maturation and survival of oligodendrocytes in vitro. Development 120 143-153. 

Moran, C.S., Campbell, J.H., Simmons, D.L. and Campbell, G.R. (1994) Human leukemia inhibitory factor inhibits development of experimental atherosclerosis. Arterioscler. Thromb. 14 1356-1363. 

Mori, M., Yamaguchi, K., Honda, S., Nagasaki, K., Ueda, M., Abe, O. and Abe, K. (1991) Cancer cachexia syndrome developed in nude mice bearing melanoma cells producing leukemia inhibitory factor. Cancer Res. 51 6656-6659. 

Richards, L.J., Kilpatrick, T.J., Bartlett, P.F. and Murphy, M. (1992) Leukemia inhibitory factor promotes the neuronal development of spinal cord precursors from the neural tube. J. Neurosci. Res. 33 476-484. 

The receptor for CNTF has recently been cloned (Davis et al., 1991) and appears to be exclusively expressed in the nervous system and in skeletal muscle. In contrast to other known receptors, the receptor for CNTF is anchored to the plasma membrane by a glycosyl-phospha-tidylinositol linkage (Davis et al., 1991). Its primary structure is most similar to the IL-6 receptor. Furthermore, both CNTF and the structurally related leukemia-inhibitory factor (see above) use the IL-6 signal transducer gpl30 (Ip et al., 1992). These observations raise the possibility that the receptors for CNTF, leukemia-inhibitory factor and hematopoietic cytokines are able to interact with each other and to activate related signaling pathways in diverse cell types (Bazan, 1991 Davis and Yancopoulos, 1993). It has been shown by Lillien et al. (1990) that some biological functions of CNTF, e.g. induction of type-2 astrocyte development, require cooperation with as yet unknown ECM-associated molecule(s). 

Promotes neuron development and preservation Binds to and activates glycoprotein 130 and leukemia inhibitory factor receptor member 3 induces tyrosine phosphorylation of these receptors... 

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