Functions and molecular mechanisms of the CD47–SIRPα signalling pathway

Signal regulatory protein (SIRP)α, also known as SHPS-1 or SIRPA, is a transmembrane protein that binds to the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region and is predominantly expressed in neurons, dendritic cells and macrophages. CD47, a widely expressed transmembrane protein, is a ligand for SIRPα, with the two proteins constituting a cell–cell communication system. The interaction of SIRPα with CD47 is important for the regulation of migration and phagocytosis. Recent studies have implicated the CD47–SIRPα signalling pathway in immune homeostasis and in regulation of neuronal networks. Advances in the structural and functional analyses of the CD47–SIRPα signalling pathway now provide exciting hints of the therapeutic benefits of manipulating this signalling system in autoimmune diseases and neurological disorders.