Abstract
Leukemia Inhibitory Factor (LIF) interacts with two classes of high affinity binding sites on rat UMR cells cultured in monolayer. One class of binding sites was found to be localized in the extracellular matrix (ECM) after removal of cells from the culture dish. The interaction of LIF with ECM-localized binding sites is not dependent upon either glycosylation of LIF or the presence of extracellular glycosyaminoglycans. Chemical cross-linking studies demonstrate that LIF interacts with a 200-kD cell-associated protein and a 140-kD ECM- localized protein. A 140-kD protein could also be specifically precipitated from solubilised metabolically radiolabeled UMR ECM by antibodies directed against LIF by virtue of its ability to form a stable complex with unlabeled LIF. In addition, soluble LIF associated with this ECM-localized protein is biologically active in terms of inhibition of ES cell differentiation. The properties of ECM-localized 140-kD species are very similar to those of the secreted form of the LIF receptor suggesting that the ECM localization of LIF and LIF signal transduction may be closely coupled.
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- Allan E. H., Hilton D. J., Brown M. A., Evely R. S., Yumita S., Metcalf D., Gough N. M., Ng K. W., Nicola N. A., Martin T. J. Osteoblasts display receptors for and responses to leukemia-inhibitory factor. J Cell Physiol. 1990 Oct;145(1):110–119. doi: 10.1002/jcp.1041450116. [DOI] [PubMed] [Google Scholar]
- Andres J. L., Stanley K., Cheifetz S., Massagué J. Membrane-anchored and soluble forms of betaglycan, a polymorphic proteoglycan that binds transforming growth factor-beta. J Cell Biol. 1989 Dec;109(6 Pt 1):3137–3145. doi: 10.1083/jcb.109.6.3137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baumann H., Wong G. G. Hepatocyte-stimulating factor III shares structural and functional identity with leukemia-inhibitory factor. J Immunol. 1989 Aug 15;143(4):1163–1167. [PubMed] [Google Scholar]
- Berstine E. G., Hooper M. L., Grandchamp S., Ephrussi B. Alkaline phosphatase activity in mouse teratoma. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3899–3903. doi: 10.1073/pnas.70.12.3899. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bruce A. G., Hoggatt I. H., Rose T. M. Oncostatin M is a differentiation factor for myeloid leukemia cells. J Immunol. 1992 Aug 15;149(4):1271–1275. [PubMed] [Google Scholar]
- Conquet F., Peyriéras N., Tiret L., Brûlet P. Inhibited gastrulation in mouse embryos overexpressing the leukemia inhibitory factor. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8195–8199. doi: 10.1073/pnas.89.17.8195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
- Fukunaga R., Ishizaka-Ikeda E., Seto Y., Nagata S. Expression cloning of a receptor for murine granulocyte colony-stimulating factor. Cell. 1990 Apr 20;61(2):341–350. doi: 10.1016/0092-8674(90)90814-u. [DOI] [PubMed] [Google Scholar]
- Gearing D. P., Comeau M. R., Friend D. J., Gimpel S. D., Thut C. J., McGourty J., Brasher K. K., King J. A., Gillis S., Mosley B. The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor. Science. 1992 Mar 13;255(5050):1434–1437. doi: 10.1126/science.1542794. [DOI] [PubMed] [Google Scholar]
- Gearing D. P., Thut C. J., VandeBos T., Gimpel S. D., Delaney P. B., King J., Price V., Cosman D., Beckmann M. P. Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130. EMBO J. 1991 Oct;10(10):2839–2848. doi: 10.1002/j.1460-2075.1991.tb07833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Godard A., Heymann D., Raher S., Anegon I., Peyrat M. A., Le Mauff B., Mouray E., Gregoire M., Virdee K., Soulillou J. P. High and low affinity receptors for human interleukin for DA cells/leukemia inhibitory factor on human cells. Molecular characterization and cellular distribution. J Biol Chem. 1992 Feb 15;267(5):3214–3222. [PubMed] [Google Scholar]
- Goodwin R. G., Friend D., Ziegler S. F., Jerzy R., Falk B. A., Gimpel S., Cosman D., Dower S. K., March C. J., Namen A. E. Cloning of the human and murine interleukin-7 receptors: demonstration of a soluble form and homology to a new receptor superfamily. Cell. 1990 Mar 23;60(6):941–951. doi: 10.1016/0092-8674(90)90342-c. [DOI] [PubMed] [Google Scholar]
- Heath J. K., Smith A. G., Hsu L. W., Rathjen P. D. Growth and differentiation factors of pluripotential stem cells. J Cell Sci Suppl. 1990;13:75–85. doi: 10.1242/jcs.1990.supplement_13.8. [DOI] [PubMed] [Google Scholar]
- Hilton D. J., Nicola N. A., Metcalf D. Distribution and comparison of receptors for leukemia inhibitory factor on murine hemopoietic and hepatic cells. J Cell Physiol. 1991 Feb;146(2):207–215. doi: 10.1002/jcp.1041460204. [DOI] [PubMed] [Google Scholar]
- Hilton D. J., Nicola N. A., Metcalf D. Specific binding of murine leukemia inhibitory factor to normal and leukemic monocytic cells. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5971–5975. doi: 10.1073/pnas.85.16.5971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ip N. Y., Nye S. H., Boulton T. G., Davis S., Taga T., Li Y., Birren S. J., Yasukawa K., Kishimoto T., Anderson D. J. CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130. Cell. 1992 Jun 26;69(7):1121–1132. doi: 10.1016/0092-8674(92)90634-o. [DOI] [PubMed] [Google Scholar]
- Ip N. Y., Yancopoulos G. D. Ciliary neurotrophic factor and its receptor complex. Prog Growth Factor Res. 1992;4(2):139–155. doi: 10.1016/0955-2235(92)90028-g. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Layton M. J., Cross B. A., Metcalf D., Ward L. D., Simpson R. J., Nicola N. A. A major binding protein for leukemia inhibitory factor in normal mouse serum: identification as a soluble form of the cellular receptor. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8616–8620. doi: 10.1073/pnas.89.18.8616. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maliszewski C. R., Sato T. A., Vanden Bos T., Waugh S., Dower S. K., Slack J., Beckmann M. P., Grabstein K. H. Cytokine receptors and B cell functions. I. Recombinant soluble receptors specifically inhibit IL-1- and IL-4-induced B cell activities in vitro. J Immunol. 1990 Apr 15;144(8):3028–3033. [PubMed] [Google Scholar]
- Matsui Y., Zsebo K., Hogan B. L. Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell. 1992 Sep 4;70(5):841–847. doi: 10.1016/0092-8674(92)90317-6. [DOI] [PubMed] [Google Scholar]
- Metcalf D., Gearing D. P. Fatal syndrome in mice engrafted with cells producing high levels of the leukemia inhibitory factor. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5948–5952. doi: 10.1073/pnas.86.15.5948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moreau J. F., Donaldson D. D., Bennett F., Witek-Giannotti J., Clark S. C., Wong G. G. Leukaemia inhibitory factor is identical to the myeloid growth factor human interleukin for DA cells. Nature. 1988 Dec 15;336(6200):690–692. doi: 10.1038/336690a0. [DOI] [PubMed] [Google Scholar]
- Mori M., Yamaguchi K., Abe K. Purification of a lipoprotein lipase-inhibiting protein produced by a melanoma cell line associated with cancer cachexia. Biochem Biophys Res Commun. 1989 May 15;160(3):1085–1092. doi: 10.1016/s0006-291x(89)80114-7. [DOI] [PubMed] [Google Scholar]
- Mosley B., Beckmann M. P., March C. J., Idzerda R. L., Gimpel S. D., VandenBos T., Friend D., Alpert A., Anderson D., Jackson J. The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms. Cell. 1989 Oct 20;59(2):335–348. doi: 10.1016/0092-8674(89)90295-x. [DOI] [PubMed] [Google Scholar]
- Munson P. J., Rodbard D. Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem. 1980 Sep 1;107(1):220–239. doi: 10.1016/0003-2697(80)90515-1. [DOI] [PubMed] [Google Scholar]
- Rathjen P. D., Nichols J., Toth S., Edwards D. R., Heath J. K., Smith A. G. Developmentally programmed induction of differentiation inhibiting activity and the control of stem cell populations. Genes Dev. 1990 Dec;4(12B):2308–2318. doi: 10.1101/gad.4.12b.2308. [DOI] [PubMed] [Google Scholar]
- Rathjen P. D., Toth S., Willis A., Heath J. K., Smith A. G. Differentiation inhibiting activity is produced in matrix-associated and diffusible forms that are generated by alternate promoter usage. Cell. 1990 Sep 21;62(6):1105–1114. doi: 10.1016/0092-8674(90)90387-t. [DOI] [PubMed] [Google Scholar]
- Rheinwald J. G., Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975 Nov;6(3):331–343. doi: 10.1016/s0092-8674(75)80001-8. [DOI] [PubMed] [Google Scholar]
- Saksela O., Rifkin D. B. Release of basic fibroblast growth factor-heparan sulfate complexes from endothelial cells by plasminogen activator-mediated proteolytic activity. J Cell Biol. 1990 Mar;110(3):767–775. doi: 10.1083/jcb.110.3.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith A. G., Heath J. K., Donaldson D. D., Wong G. G., Moreau J., Stahl M., Rogers D. Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature. 1988 Dec 15;336(6200):688–690. doi: 10.1038/336688a0. [DOI] [PubMed] [Google Scholar]
- Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
- Stewart C. L., Kaspar P., Brunet L. J., Bhatt H., Gadi I., Köntgen F., Abbondanzo S. J. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature. 1992 Sep 3;359(6390):76–79. doi: 10.1038/359076a0. [DOI] [PubMed] [Google Scholar]
- Taga T., Hibi M., Hirata Y., Yamasaki K., Yasukawa K., Matsuda T., Hirano T., Kishimoto T. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell. 1989 Aug 11;58(3):573–581. doi: 10.1016/0092-8674(89)90438-8. [DOI] [PubMed] [Google Scholar]
- Takaki S., Tominaga A., Hitoshi Y., Mita S., Sonoda E., Yamaguchi N., Takatsu K. Molecular cloning and expression of the murine interleukin-5 receptor. EMBO J. 1990 Dec;9(13):4367–4374. doi: 10.1002/j.1460-2075.1990.tb07886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vlodavsky I., Folkman J., Sullivan R., Fridman R., Ishai-Michaeli R., Sasse J., Klagsbrun M. Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2292–2296. doi: 10.1073/pnas.84.8.2292. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamamori T., Fukada K., Aebersold R., Korsching S., Fann M. J., Patterson P. H. The cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor. Science. 1989 Dec 15;246(4936):1412–1416. doi: 10.1126/science.2512641. [DOI] [PubMed] [Google Scholar]