Leukemia inhibitory factor structure

FIGURE 27-3 Neurotrophic cytokines and their receptors. Neurotrophic cytokines are related to IL6 and bind to cell surface receptor complexes that share a common structural organization. The four ligands interchangeably employ two distinct receptor subunits, leukemia inhibitory factor receptor 3 (LIF-Rpt) andgpl30, and some employ a ligand-specific a subunit. CNTF-R, ciliary neurotrophic factor CT-fR.cardiotrophin 1 receptor IL6-R, interleukin-6 receptor. 

Fig. 11.2. Domain structure of cytokine receptors. Schematic representation of the domain structure of selected cytokine receptors. WS motif conserved WSXWS sequence (W tryptophan S serine X non-conserved amino add) IL interleukin EpoR receptor for erythropoietin GHR growth hormone receptor LIF-R leukemia inhibitory factor receptor G-CSFR granulocyte colony stimulating factor receptor IFNR interferon receptor TNFR tumor necrosis factor receptor NGFR nerve growth factor receptor Fas, CD40 transmembrane receptors of lymphocytes.

Fig. 11.3. Subunit structures of cytokine receptors. EpoR and G-CSFR have a homo-oligomeric structure. The other receptors shown are composed of different subunits, some of which occur in several receptors. The gpl30 subunit is common to IL-6R and LIF-R the Yc subunit is found in IL-2R and IL-4R. The subunits, at which ligand binding occurs, are indicated by arrows. LIF-R leukemia inhibitory factor receptor.

Fig. 3. The gplSO family of cytokines and receptors. Schematic representation of gpl30 and leukemia inhibitory factor receptor (LIFR) oriented in a cell membrane. Of the four-helix bundle gplSO cytokines, structural information currently exists for human interleukin 6 (IL-6) (green) (Somers et al, 1997), human herpes virus interleukin 6 (HlTV-8 IL-6) (purple) (Chow et al, 2001a), ciliary neurotrophic factor (CNTF) (orange) (McDonald et al., 1995), leukemia inhibitory factor (LIF) (blue) (Robinson et al, 1994), and oncostatin-M (OSM) (red) (Deller et al, 2000). Lower panel is a detailed list of gplSO cytokines and the associated receptors incorporated into the final signaling complex. (See Color Insert.)...

Plun-Favreau, H., Ferret, D., Diveu, C., Froger, J., Chevalier, S., Lelievre, E., Gascan, H., and Chabbert, M. (2003). Leukemia inhibitory factor (LIF), cardiotrophin-1, and oncostatin M share structural binding determinants in the immunoglobulin-like domain of LIF receptor./. Biol. Chem. 278, 27169-27179. 

B16. Baumann, H., and Wong, G. G. Hepatocyte-stimulating factor III shares structural and functional identity with leukemia-inhibitory factor. 7. Immunol. 143, 1163-1167 (1989). 

Gearing, D.P., Thut, C.J., VandeBos, T., Gimpel, S.D., Delaney, P.B., King, J., Price, V., Cosman, D. and Beckmann, M.P. (1991) Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gpl30. EMBO... 

Robinson, R.C., Grey, L.M., Staunton, D., Vankelecom, H., Vernallis, A.B., Moreau, J.-F., Stuart, D.I., Heath, J.K, and Jones, E.Y. (1994) The crystal structure and biological function of leukemia inhibitory factor implications for receptor binding. Cell 77 1101-1116. 

Stahl, J., Gearing, D.P., Willson, T.A., Brown, M.A., King, J.A. and Gough, N.M. (1990) Structural organization of the genes for murine and human leukemia inhibitory factor. J. 

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). 

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