Functions and molecular mechanisms of the CD47-SIRPalpha signalling pathway.

Signal regulatory protein (SIRP)alpha, 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 SIRPalpha, with the two proteins constituting a cell-cell communication system. The interaction of SIRPalpha with CD47 is important for the regulation of migration and phagocytosis. Recent studies have implicated the CD47-SIRPalpha signalling pathway in immune homeostasis and in regulation of neuronal networks. Advances in the structural and functional analyses of the CD47-SIRPalpha signalling pathway now provide exciting hints of the therapeutic benefits of manipulating this signalling system in autoimmune diseases and neurological disorders.