Recombinant Human SIRPα-Fc Chimera (carrier-free)

Signal Regulatory Proteins (SIRPs) are a family of transmembrane glycoproteins with extracellular IgG domains. SIRPα is an inhibitory receptor expressed on neurons and myeloid cells, including macrophages, granulocytes, myeloid dendritic cells, mast cells, and their precursors (including hematopoietic stem cells). The extracellular regions of the SIRPs are comprised of three Ig-like loops; the proximal loops contain IgC domains, whereas the distal membrane loop contains an IgV domain. While these extracellular domains are fairly similar between SIRPs, their transmembrane and cytoplasmic domains differentiate them from one another. The C-terminal intracellular domains of the SIRPα subfamily contain a relatively long amino acid sequence that includes four tyrosine residues to form two immunoreceptor tyrosine-based inhibition motifs (ITIM). SIRPα is best known for its inhibitory role following its interaction with the widely distributed protein CD47 (on host target cells). CD47 is a “marker of self”, which upon binding to SIRPα signals against phagocytosis by macrophages expressing SIRPα. When CD47 binds the N-terminal IgG domain of SIRPα, this causes clustering and phosphorylation of SIRPα. SIRPα phosphorylation results in the recruitment and activation of the tyrosine phosphatases SHP-1 and SHP-2, which regulate cellular functions in a negative fashion, including the regulation of leukocyte adhesion and transmigration, T cell activation, macrophage fusion and phagocytosis. In addition to its role in "self-signaling", SIRPα also functions as a scaffold for membrane-bound signaling molecules, plays a role in macrophage and osteoclast fusion, regulates T cell/DC activation and controls myeloid cell migration.