Signal regulatory proteins: Introduction

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Signal regulatory proteins (SIRPs; also known as myeloid-paired receptors) are leukocyte-expressed membrane proteins that are involved in regulation of immune cells to ensure an optimal immune response to pathogens, but at the same time minimising self damage. They are also CD (cluster of differentiation) proteins. The extracellular regions of SIRP family members share significant homology, but exhibit different signalling potentials, with each family member mediating either an activating or inhibititory signal. In humans 5 SIRP genes (and one pseudogene) have been identified: SIRPA (SIRPα; CD172a), SIRPB1 (SIRPβ1; CD172b), SIRPB2, SIRPD and SIRPG (SIRPγ; CD172g). They are listed in HGNC family 747.

SIRPs associate with other proteins to achieve their regulatory effects. One well established interaction is that between the inhibitory SIRPα protein and CD47, an interaction that acts as an immune checkpoint. SIRPα/CD47 blockade is being exploited as an immuno-oncology strategy [5], by inhibiting either SIRPα [4] or CD47 [1,3]. Note that developing monoclonal antibodies that are selective for specific SIRPs is difficult because of their structural similarities, and because each gene is polymorphic [2].

References

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1. Gholamin S, Mitra SS, Feroze AH, Liu J, Kahn SA, Zhang M, Esparza R, Richard C, Ramaswamy V, Remke M et al.. (2017) Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors. Sci Transl Med, 9 (381). [PMID:28298418]

2. Hatherley D, Aknin ML, Barclay AN. (2016) OX130 Monoclonal Antibody Recognizes Human SIRPβ1 but Cross-Reacts on SIRPα from One Allele. Monoclon Antib Immunodiagn Immunother, 35 (1): 57-9. [PMID:26871367]

3. Li F, Lv B, Liu Y, Hua T, Han J, Sun C, Xu L, Zhang Z, Feng Z, Cai Y et al.. (2018) Blocking the CD47-SIRPα axis by delivery of anti-CD47 antibody induces antitumor effects in glioma and glioma stem cells. Oncoimmunology, 7 (2): e1391973. [PMID:29308321]

4. Liu Q, Wen W, Tang L, Qin CJ, Lin Y, Zhang HL, Wu H, Ashton C, Wu HP, Ding J et al.. (2016) Inhibition of SIRPα in dendritic cells potentiates potent antitumor immunity. Oncoimmunology, 5 (9): e1183850. [PMID:27757296]

5. Veillette A, Chen J. (2018) SIRPα-CD47 Immune Checkpoint Blockade in Anticancer Therapy. Trends Immunol., 39 (3): 173-184. [PMID:29336991]

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To cite this family introduction, please use the following:

Signal regulatory proteins, introduction. Last modified on 06/03/2018. Accessed on 17/01/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=989.