The receptor gp130 is used by the interleukin-6 (IL-6)-type cytokines, which include IL-6 and leukaemia-inhibitory factor (LIF). To investigate the role of the three extracellular membrane-proximal fibronectin-type-III-like (FNIII) modules of gp130 and the related receptor for granulocyte colony-stimulating factor (G-CSFR) in cytokine signal transduction we have transfected into murine myeloid M1-UR21 cells the chimaera (GR-FNIII)gp130, which contains the membrane-proximal FNIII modules of the G-CSFR on a gp130 backbone, and its complement, the chimaera (gp130-FNIII)GR. Whereas the binding affinities of 125I-labelled IL-6 to (GR-FNIII)gp130, or of 125I-Tyr1,3-G-CSF to (gp130-FNIII)GR, were similar to wild-type gp130 and wild-type G-CSFR, respectively, 125I-LIF failed to bind with high affinity to (GR-FNIII)gp130. In assays measuring differentiation the (gp130-FNIII)GR cells were fully responsive to G-CSF, whereas the (GR-FNIII)gp130 cells responded fully to the agonistic anti-gp130 monoclonal antibody (mAb) B-S12, but not to IL-6 or LIF. Neutralizing mAbs that recognize the membrane-proximal FNIII modules of gp130 or the G-CSFR differentially interfered with signalling by B-S12, LIF and G-CSF. The data suggest that B-S12 and G-CSF induce the correct orientation or conformation for signalling by the wild-type and chimaeric homodimeric receptors, that the membrane-proximal region of gp130 is important for the correct formation of the signalling IL-6-IL-6 receptor-gp130 complex and that this region is also involved in LIF-dependent receptor heterodimerization and signalling.
Skip Nav Destination
Article navigation
January 2000
-
Cover Image
Cover Image
- PDF Icon PDF LinkTable of Contents
Research Article|
December 17 1999
Ligand-specific utilization of the extracellular membrane-proximal region of the gp130-related signalling receptors
Annet HAMMACHER;
Annet HAMMACHER
*Ludwig Institute for Cancer Research, P.O. Box 2008, Royal Melbourne Hospital, Victoria 3050, Australia
†Cooperative Research Centre for Cellular Growth Factors, P.O. Royal Melbourne Hospital, 3050 Victoria, Australia
Search for other works by this author on:
John WIJDENES;
John WIJDENES
‡DIACLONE, 1, Bd. Fleming - B.P. 1985, F-25020 Besançon Cedex, France
Search for other works by this author on:
Douglas J. HILTON;
Douglas J. HILTON
†Cooperative Research Centre for Cellular Growth Factors, P.O. Royal Melbourne Hospital, 3050 Victoria, Australia
§The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, 3050, Victoria, Australia
Search for other works by this author on:
Nicos A. NICOLA;
Nicos A. NICOLA
†Cooperative Research Centre for Cellular Growth Factors, P.O. Royal Melbourne Hospital, 3050 Victoria, Australia
§The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, 3050, Victoria, Australia
Search for other works by this author on:
Richard J. SIMPSON;
Richard J. SIMPSON
†Cooperative Research Centre for Cellular Growth Factors, P.O. Royal Melbourne Hospital, 3050 Victoria, Australia
¶Joint Protein Structure Laboratory, Ludwig Institute for Cancer Research/The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, 3050 Victoria, Australia
Search for other works by this author on:
Judith E. LAYTON
Judith E. LAYTON
*Ludwig Institute for Cancer Research, P.O. Box 2008, Royal Melbourne Hospital, Victoria 3050, Australia
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
August 03 1999
Revision Received:
September 30 1999
Accepted:
October 28 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2000
2000
Biochem J (2000) 345 (1): 25–32.
Article history
Received:
August 03 1999
Revision Received:
September 30 1999
Accepted:
October 28 1999
Citation
Annet HAMMACHER, John WIJDENES, Douglas J. HILTON, Nicos A. NICOLA, Richard J. SIMPSON, Judith E. LAYTON; Ligand-specific utilization of the extracellular membrane-proximal region of the gp130-related signalling receptors. Biochem J 1 January 2000; 345 (1): 25–32. doi: https://doi.org/10.1042/bj3450025
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.