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Interleukin-6 (IL-6) induces growth arrest and macrophage differentiation through its receptor in a murine myeloid leukaemic cell line, M1, although it is largely unknown how the IL-6 receptor generates these signals. By using chimeric receptors consisting of the extracellular domain of growth hormone receptor and the transmembrane and cytoplasmic domain of gp130 with progressive C-terminal truncations, we showed that the membrane-proximal 133, but not 108, amino acids of gp130 could generate the signals for growth arrest, macrophage differentiation, down-regulation of c-myc and c-myb, induction of junB and IRF1 and Stat3 activation. Mutational analysis of this region showed that the tyrosine residue with the YXXQ motif was critical not only for Stat3 activation but also for growth arrest and differentiation, accompanied by down-regulation of c-myc and c-myb and immediate early induction of junB and IRF1. The tight correlation between Stat3 activation and other IL-6 functions was further observed in the context of the full-length cytoplasmic region of gp130. The result suggest that Stat3 plays an essential role in the signals for growth arrest and differentiation.

Titel:	Differentiation and growth arrest signals are generated through the cytoplasmic region of gp130 that is essential for Stat3 activation.
Autor/in / Beteiligte Person:	Yamanaka, Y ; Nakajima, K ; Fukada, T ; Hibi, M ; Hirano, T
Zeitschrift:	The EMBO journal, Jg. 15 (1996-04-01), Heft 7, S. 1557-65
Veröffentlichung:	2024- : [London] : Nature Publishing Group ; <i>Original Publication</i>: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-, 1996
Medientyp:	academicJournal
ISSN:	0261-4189 (print)
Schlagwort:	Amino Acid Sequence Animals Antigens, CD chemistry Antigens, CD genetics Cell Line Cytokine Receptor gp130 Cytoplasm chemistry Gene Expression Regulation Interleukin-6 physiology Membrane Glycoproteins chemistry Membrane Glycoproteins genetics Mice Molecular Sequence Data Molecular Structure Recombinant Fusion Proteins chemistry Recombinant Fusion Proteins genetics Recombinant Fusion Proteins physiology STAT3 Transcription Factor Signal Transduction Tyrosine chemistry Antigens, CD physiology Cell Differentiation physiology Cell Division physiology DNA-Binding Proteins physiology Membrane Glycoproteins physiology Trans-Activators physiology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [EMBO J] 1996 Apr 01; Vol. 15 (7), pp. 1557-65. MeSH Terms: Antigens, CD / physiology ; Cell Differentiation / physiology ; Cell Division / physiology ; DNA-Binding Proteins / physiology ; Membrane Glycoproteins / physiology ; Trans-Activators / physiology ; Amino Acid Sequence ; Animals ; Antigens, CD / chemistry ; Antigens, CD / genetics ; Cell Line ; Cytokine Receptor gp130 ; Cytoplasm / chemistry ; Gene Expression Regulation ; Interleukin-6 / physiology ; Membrane Glycoproteins / chemistry ; Membrane Glycoproteins / genetics ; Mice ; Molecular Sequence Data ; Molecular Structure ; Recombinant Fusion Proteins / chemistry ; Recombinant Fusion Proteins / genetics ; Recombinant Fusion Proteins / physiology ; STAT3 Transcription Factor ; Signal Transduction ; Tyrosine / chemistry References: FEBS Lett. 1988 Jul 4;234(1):17-21. (PMID: 3292283) ; Gene Ther. 1994 Mar;1(2):136-8. (PMID: 7584069) ; Proc Natl Acad Sci U S A. 1988 Nov;85(21):8037-41. (PMID: 3054878) ; Blood. 1988 Dec;72(6):2070-3. (PMID: 3264198) ; Cell. 1989 Aug 11;58(3):573-81. (PMID: 2788034) ; Annu Rev Immunol. 1990;8:253-78. (PMID: 2188664) ; Cell. 1990 Dec 21;63(6):1149-57. (PMID: 2261637) ; Mol Cell Biol. 1991 May;11(5):2375-81. (PMID: 1901940) ; Oncogene. 1991 Jun;6(6):903-9. (PMID: 1906157) ; Mol Cell Biol. 1991 Sep;11(9):4371-9. (PMID: 1908551) ; Science. 1991 Nov 8;254(5033):821-5. (PMID: 1948064) ; Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11349-53. (PMID: 1662392) ; Chem Immunol. 1992;51:153-80. (PMID: 1567541) ; Mol Cell Biol. 1992 Jun;12(6):2493-500. (PMID: 1588953) ; Cell. 1992 Jun 26;69(7):1121-32. (PMID: 1617725) ; Science. 1992 Aug 7;257(5071):809-13. (PMID: 1496401) ; Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7836-9. (PMID: 1502203) ; EMBO J. 1992 Oct;11(10):3541-9. (PMID: 1396555) ; Blood. 1992 Nov 1;80(9):2298-305. (PMID: 1384800) ; J Cell Biochem. 1992 Sep;50(1):1-9. (PMID: 1385455) ; Mol Cell Biol. 1993 Jan;13(1):276-88. (PMID: 7678052) ; Cell. 1993 Jan 29;72(2):197-209. (PMID: 7678779) ; Mol Cell Biol. 1993 Apr;13(4):2384-90. (PMID: 7681146) ; Mol Cell Biol. 1993 May;13(5):3027-41. (PMID: 8386318) ; Science. 1993 Jun 18;260(5115):1805-8. (PMID: 8390097) ; Science. 1993 Jun 18;260(5115):1808-10. (PMID: 8511589) ; J Immunol. 1993 Sep 1;151(5):2555-61. (PMID: 8360477) ; Science. 1993 Sep 24;261(5129):1730-3. (PMID: 8378773) ; Science. 1993 Sep 24;261(5129):1736-9. (PMID: 8378775) ; Science. 1993 Sep 24;261(5129):1739-44. (PMID: 8397445) ; Blood. 1993 Oct 1;82(7):1960-74. (PMID: 8400249) ; Cell. 1993 Sep 24;74(6):1079-87. (PMID: 7691413) ; EMBO J. 1993 Nov;12(11):4181-9. (PMID: 8223433) ; Science. 1993 Dec 3;262(5139):1575-9. (PMID: 7504325) ; Mol Cell Biol. 1994 Jan;14(1):138-46. (PMID: 8264582) ; Science. 1994 Jan 7;263(5143):92-5. (PMID: 8272873) ; Mol Cell Biol. 1994 Apr;14(4):2352-60. (PMID: 8139540) ; Science. 1994 Apr 1;264(5155):95-8. (PMID: 8140422) ; Cell. 1994 Apr 8;77(1):63-71. (PMID: 7512451) ; J Biol Chem. 1994 Apr 15;269(15):11648-55. (PMID: 7512571) ; J Immunol. 1982 Apr;128(4):1903-8. (PMID: 6801125) ; Science. 1986 Aug 1;233(4763):566-9. (PMID: 3726549) ; Nature. 1986 Nov 6-12;324(6092):73-6. (PMID: 3491322) ; FEBS Lett. 1987 Aug 31;221(1):18-22. (PMID: 3305075) ; Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251-5. (PMID: 2444978) ; Nature. 1988 Mar 3;332(6159):83-5. (PMID: 3258060) ; EMBO J. 1994 Apr 15;13(8):1942-9. (PMID: 8168491) ; Biochem Biophys Res Commun. 1994 Apr 29;200(2):821-8. (PMID: 8179617) ; Science. 1994 Jun 3;264(5164):1415-21. (PMID: 8197455) ; Biochem Biophys Res Commun. 1994 Jul 29;202(2):1181-7. (PMID: 7519422) ; Stem Cells. 1994 May;12(3):262-77. (PMID: 8075593) ; J Biol Chem. 1994 Nov 25;269(47):29962-9. (PMID: 7961995) ; EMBO J. 1995 Jan 16;14(2):266-75. (PMID: 7835337) ; Science. 1995 Feb 17;267(5200):1018-21. (PMID: 7863327) ; Science. 1995 Feb 17;267(5200):1024-7. (PMID: 7863329) ; Science. 1995 Mar 3;267(5202):1349-53. (PMID: 7871433) ; Oncogene. 1995 Mar 2;10(5):985-94. (PMID: 7898939) ; Science. 1995 Apr 14;268(5208):251-5. (PMID: 7716517) ; Trends Genet. 1995 Feb;11(2):69-74. (PMID: 7716810) ; Cell. 1995 Apr 21;81(2):223-31. (PMID: 7736574) ; Ann N Y Acad Sci. 1995 Jul 21;762:55-70. (PMID: 7545378) ; Science. 1988 Aug 12;241(4867):825-8. (PMID: 3136546) Substance Nomenclature: 0 (Antigens, CD) ; 0 (DNA-Binding Proteins) ; 0 (Il6st protein, mouse) ; 0 (Interleukin-6) ; 0 (Membrane Glycoproteins) ; 0 (Recombinant Fusion Proteins) ; 0 (STAT3 Transcription Factor) ; 0 (Stat3 protein, mouse) ; 0 (Trans-Activators) ; 133483-10-0 (Cytokine Receptor gp130) ; 42HK56048U (Tyrosine) Entry Date(s): Date Created: 19960401 Date Completed: 19960606 Latest Revision: 20181113 Update Code: 20240513 PubMed Central ID: PMC450065

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Differentiation and growth arrest signals are generated through the cytoplasmic region of gp130 that is essential for Stat3 activation.