| Structural highlights
Function
[SHPS1_HUMAN] Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function (By similarity). Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells.[1] [2] [CD47_HUMAN] Has a role in both cell adhesion by acting as an adhesion receptor for THBS1 on platelets, and in the modulation of integrins. Plays an important role in memory formation and synaptic plasticity in the hippocampus (By similarity). Receptor for SIRPA, binding to which prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-dependent T-cell-mediated proliferation and costimulates T-cell activation. May play a role in membrane transport and/or integrin dependent signal transduction. May prevent premature elimination of red blood cells. May be involved in membrane permeability changes induced following virus infection.[3] [4] [5]
Publication Abstract from PubMed
CD47 is a widely distributed membrane protein that interacts with Signal-regulatory protein alpha (SIRPalpha), an inhibitory receptor on myeloid cells that gives a do-not-eat-me signal. Manipulation of the interaction is of considerable interest in the immunotherapy of cancer and in xenotransplantation. The amino terminal ligand binding domain of SIRPalpha is highly polymorphic in contrast to the single Ig-like domain of CD47. There is confusion as to whether the polymorphisms will affect ligand binding but this is an important point for this interaction and other paired receptors being considered for as targets for therapy. We show by X-ray crystallography that one human SIRPalpha allele differing in 13 amino acid residues has a very similar binding site and that several different alleles all bind CD47 with similar affinity as expected as the residues are mostly surface exposed and distant from the binding site. A peptide from the binding site of CD47 has been reported to mimic the CD47 interaction with SIRPalpha but we could find no binding. We discuss the possible pitfalls in determining the affinity of weak interactions and also speculate on how SIRPalpha polymorphisms may have been selected by pathogens and how this may also be true in other paired receptors such as the KIRs.
Polymorphisms in the human inhibitory signal-regulatory protein alpha do not affect binding to its ligand CD47.,Hatherley D, Lea SM, Johnson S, Barclay AN J Biol Chem. 2014 Feb 19. PMID:24550402[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Timms JF, Swanson KD, Marie-Cardine A, Raab M, Rudd CE, Schraven B, Neel BG. SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-protein complexes in macrophages. Curr Biol. 1999 Aug 26;9(16):927-30. PMID:10469599
- ↑ Latour S, Tanaka H, Demeure C, Mateo V, Rubio M, Brown EJ, Maliszewski C, Lindberg FP, Oldenborg A, Ullrich A, Delespesse G, Sarfati M. Bidirectional negative regulation of human T and dendritic cells by CD47 and its cognate receptor signal-regulator protein-alpha: down-regulation of IL-12 responsiveness and inhibition of dendritic cell activation. J Immunol. 2001 Sep 1;167(5):2547-54. PMID:11509594
- ↑ Lindberg FP, Gresham HD, Schwarz E, Brown EJ. Molecular cloning of integrin-associated protein: an immunoglobulin family member with multiple membrane-spanning domains implicated in alpha v beta 3-dependent ligand binding. J Cell Biol. 1993 Oct;123(2):485-96. PMID:7691831
- ↑ Latour S, Tanaka H, Demeure C, Mateo V, Rubio M, Brown EJ, Maliszewski C, Lindberg FP, Oldenborg A, Ullrich A, Delespesse G, Sarfati M. Bidirectional negative regulation of human T and dendritic cells by CD47 and its cognate receptor signal-regulator protein-alpha: down-regulation of IL-12 responsiveness and inhibition of dendritic cell activation. J Immunol. 2001 Sep 1;167(5):2547-54. PMID:11509594
- ↑ Piccio L, Vermi W, Boles KS, Fuchs A, Strader CA, Facchetti F, Cella M, Colonna M. Adhesion of human T cells to antigen-presenting cells through SIRPbeta2-CD47 interaction costimulates T-cell proliferation. Blood. 2005 Mar 15;105(6):2421-7. Epub 2004 Sep 21. PMID:15383453 doi:10.1182/blood-2004-07-2823
- ↑ Hatherley D, Lea SM, Johnson S, Barclay AN. Polymorphisms in the human inhibitory signal-regulatory protein alpha do not affect binding to its ligand CD47. J Biol Chem. 2014 Feb 19. PMID:24550402 doi:http://dx.doi.org/10.1074/jbc.M114.550558
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