Signal regulatory protein alpha (SIRPalpha)/CD47 interaction and function.
1Sir William Dunn School of Pathology, University of Oxford, United Kingdom. neil.barclay@path.ox.ac.uk
Current Opinion in Immunology
|February 19, 2009
Summary
The SIRPalpha receptor on myeloid cells binds CD47, regulating cell signaling. This review explores the SIRPalpha/CD47 interaction, its structural basis, and implications for immune responses.
Area of Science:
- Immunology
- Cell Biology
- Structural Biology
Background:
- SIRPalpha is an inhibitory receptor on myeloid cells.
- It interacts with the CD47 protein, a widely distributed membrane protein.
- SIRPbeta, an activating receptor with sequence similarity to SIRPalpha, does not bind CD47.
Purpose of the Study:
- To review the structural basis of the SIRPalpha/CD47 interaction.
- To explain why SIRPbeta does not bind CD47.
- To discuss polymorphisms and the evolutionary implications of these paired receptors.
Main Methods:
- Literature review of recent structural and functional data.
- Analysis of protein sequence and structural similarities/differences.
- Examination of evidence for receptor polymorphisms.
Main Results:
- The SIRPalpha/CD47 interaction allows for bidirectional signaling.
- Structural data clarifies the differential binding of SIRPalpha and SIRPbeta to CD47.
- Evidence suggests significant polymorphisms in these receptors.
Conclusions:
- The SIRPalpha-CD47 interaction is a key regulatory pathway in myeloid cells.
- Understanding the structural basis and polymorphisms is crucial for immune function.
- Further research into receptor modification by endocytosis, proteolysis, and surfactant proteins is warranted.
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