Signal regulatory protein alpha (SIRPα) (SIRPα)

Signal regulatory protein alpha (SIRPα), also known as SHPS-1, is a transmembrane glycoprotein primarily expressed on myeloid cells such as macrophages, dendritic cells, and neutrophils (UniProt P78324). It serves as a key inhibitory immune checkpoint by interacting with its ligand, CD47, which is often referred to as a "don't eat me" signal (PubMed: 29109532). Upon binding to CD47, the immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the cytoplasmic tail of SIRPα become phosphorylated, recruiting phosphatases like SHP-1 and SHP-2 to suppress phagocytosis (PubMed: 30305455). In many cancers, tumor cells overexpress CD47 to evade immune surveillance by macrophages. Therapeutic strategies targeting SIRPα aim to block this interaction, thereby "releasing the brakes" on macrophages and promoting the clearance of cancer cells (PubMed: 32631952). Unlike CD47-targeted therapies, which can cause significant anemia due to CD47 expression on red blood cells, SIRPα-targeted agents may offer a better safety profile due to the more restricted expression of the receptor (PubMed: 31515461).

Other names

SHPS-1CD172aBITP84MFRTyrosine-protein phosphatase non-receptor type substrate 1SIRPA

Antagonism of the SIRPα-CD47 interaction to enhance macrophage-mediated phagocytosis of target cells.