Signal-regulatory protein alpha (SIRPA) (SIRPA)

Signal-regulatory protein alpha (SIRPα) is a transmembrane glycoprotein primarily expressed on myeloid cells, such as macrophages and dendritic cells [1]. It functions as an inhibitory receptor that regulates the effector functions of these cells, most notably phagocytosis [2]. The primary ligand for SIRPα is CD47, a protein widely expressed on host cells and often upregulated on cancer cells to serve as a 'don't eat me' signal [3]. Upon binding to CD47, SIRPα undergoes phosphorylation of its cytoplasmic ITIM motifs, leading to the recruitment of SHP-1 and SHP-2 phosphatases that dampen pro-phagocytic signals [4]. In the context of oncology, blocking the SIRPα-CD47 interaction is a major therapeutic strategy designed to enhance the clearance of malignant cells by the innate immune system [5]. While many therapies target the CD47 ligand, specific targeting of SIRPα (via antibodies or mRNA-silencing techniques) aims to minimize off-target effects on red blood cells, which also express CD47 [6]. Clinical development includes monoclonal antibodies, SIRPα-Fc fusion proteins, and experimental siRNA approaches to modulate this checkpoint [5]. Beyond cancer, SIRPα is investigated for its roles in inflammatory and autoimmune conditions where myeloid cell activity is dysregulated [4].

Other names

CD172aSHPS-1BITMFRMYD-1PTPNS1Signal-regulatory protein alpha-1

Antagonism of the SIRPα-CD47 interaction to promote macrophage-mediated phagocytosis of tumor cells.