Signal-regulatory protein beta 1 receptor (SIRPβ1) (SIRPβ1)

Signal-regulatory protein beta 1 receptor (SIRPβ1) is a transmembrane glycoprotein belonging to the SIRP family and the immunoglobulin superfamily, predominantly expressed on myeloid cells like macrophages, neutrophils, and dendritic cells (UniProt: O00241). Unlike the inhibitory SIRPα, SIRPβ1 lacks an internal signaling domain and instead associates with the adapter protein DAP12 to transmit activating signals via immunoreceptor tyrosine-based activation motifs (ITAMs) (NCBI Gene: 10326). This interaction triggers downstream signaling pathways, including the recruitment of Syk kinase, which enhance phagocytosis and the production of pro-inflammatory cytokines (PubMed: 11160241). In therapeutic development, SIRPβ1 is being investigated as a target for cancer immunotherapy to promote the activation of tumor-associated macrophages and in neurodegenerative diseases like Alzheimer's to enhance microglial clearance of protein aggregates (PubMed: 31160581). While there are currently no FDA-approved drugs specifically targeting SIRPβ1, it remains a significant target of interest for modulating innate immune responses in various pathological conditions (PubMed: 24635070).

Other names

CD172bSIRPB1Signal-regulatory protein beta-1PTPN12L

Agonism of SIRPβ1 leads to the recruitment of DAP12 and subsequent activation of Syk kinase, promoting phagocytic activity and pro-inflammatory responses in myeloid cells (PubMed: 11160241).