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.
Matozaki
Takashi
T
Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma, Japan. matozaki@showa.gunma-u.ac.jp
Murata
Yoji
Y
Okazawa
Hideki
H
Ohnishi
Hiroshi
H
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D051928:CD47 Antigen / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000276:immunology / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology
D000943:Antigens, Differentiation; D051928:CD47 Antigen; D007328:Insulin; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6