SIRPα was initially cloned as a substrate for Src homology region 2 (SH2) domain-containing phosphatase-1 (SHP-1) and SHP-2 . These are cytoplasmic-type protein tyrosine phosphatases, and SIRPα was initially termed SHPS-1 (SHP substrate-1) . It was also named as brain immunoglobulin (Ig)-like molecule with tyrosine-based activation motifs (BIT), macrophage fusion receptor (MFR), and MyD-1 .
The extracellular region of SIRPα consists of three immunoglobulin-like domains . The cytoplasmic region comprises tyrosine residues with immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which activate SHP-1 and SHP-2, mediating the specific biological function of SIRPα . The intracellular region also binds adaptor molecules such as Src kinase-associated phosphoprotein 2 (SKAP2) and Fyn-binding protein/SLP-76-associated phosphoprotein of 130 kDa (FYB/SLAP-130), as well as the tyrosine kinase PYK2 .
SIRPα is especially expressed on neurons, pancreatic β cells, and myeloid lineage cells such as macrophages, dendritic cells, and neutrophils . Other cell types, such as fibroblasts and endothelial cells, also express SIRPα, but at lower levels . CD47, the ligand for SIRPα, is expressed in most cell types .
The interaction between SIRPα and CD47 plays a crucial role in the regulation of immune responses. SIRPα acts as an inhibitory receptor, and its interaction with CD47 helps to prevent the phagocytosis of healthy cells by macrophages . This interaction is essential for maintaining self-tolerance and preventing autoimmune responses .
SIRPα is involved in various biological processes, including cell adhesion, leukocyte migration, and the regulation of protein phosphorylation . It also plays a role in the regulation of gene expression, cell migration, and the production of cytokines such as interferon-gamma, interleukin-1 beta, interleukin-6, and tumor necrosis factor . Additionally, SIRPα is involved in the negative regulation of inflammatory responses and phagocytosis .
Recombinant SIRPα (rat) is a form of the protein that has been produced using recombinant DNA technology. This allows for the production of large quantities of the protein for research and therapeutic purposes. Recombinant SIRPα is used in various studies to understand its function and interaction with CD47, as well as its role in immune regulation and potential therapeutic applications.