The Structural Basis of the Biological Actions of the GM-CSF Receptor

  1. Gregory R. Bock Organizer and
  2. Jamie A. Goode
  1. Nicos A. Nicola,
  2. Alison Smith,
  3. Lorraine Robb,
  4. Donald Metcalf and
  5. C. Glenn Begley

Published Online: 28 SEP 2007

DOI: 10.1002/9780470515280.ch3

Ciba Foundation Symposium 204 - The Molecular Basis of Cellular Defence Mechanisms

Ciba Foundation Symposium 204 - The Molecular Basis of Cellular Defence Mechanisms

How to Cite

Nicola, N. A., Smith, A., Robb, L., Metcalf, D. and Begley, C. G. (2007) The Structural Basis of the Biological Actions of the GM-CSF Receptor, in Ciba Foundation Symposium 204 - The Molecular Basis of Cellular Defence Mechanisms (eds G. R. Bock and J. A. Goode), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470515280.ch3

Author Information

  1. The Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Victoria 3050, Australia

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471965671

Online ISBN: 9780470515280

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Keywords:

  • biological actions;
  • GM-CSF receptor;
  • signal transduction;
  • β common receptor;
  • receptor transmodulation

Summary

The receptor for granulocyte/macrophage colony-stimulating factor (GM-CSF) consists of a ligand-specific low-affinity binding chain (GM-CSFRα) and a second chain that is required for high-affinity binding and signal transduction. This second chain is shared by the ligand-specific α-chains for the interleukin 3 (IL-3) and IL-5 receptors and is therefore called β common (βc). In mice but not humans the IL-3 receptor can also use a closely related but IL-3-specific β-chain (βIL-3). In order to define the contributions of each chain to receptor signalling we generated mice in which either βc or βIL-3 expression was deleted. βIL-3 null mice were phenotypically normal but displayed a decreased responsiveness to IL-3 in vitro. βc null mice, on the other hand, were unresponsive to GM-CSF or IL-5 but still responded to IL-3. These data demonstrated that GM-CSF and IL-5 receptors can use only one β-chain for signalling (βc) while IL-3 can effectively use either β-chain. The hierarchical basis of receptor transmodulation was shown to result from this differential usage of β-chains. To define the regions required for different types of cell signalling, we constructed human βc mutants with successive cytoplasmic truncations. By the use of appropriate biological read-out systems we found that the cytoplasmic region of the receptor has a modular design with distinct domains required for cell proliferation, cell survival, differentiation and growth suppression. Appropriate targeting of these domains and the signalling pathways they initiate may provide highly specific cell therapies in the future.