Phosphorylation of ITIM in SIRP alpha SIRP alpha binds CD47 Recruitment of SHP-2 and SHP-1 to pSIRP alpha Recruitment of PYK2 to pSIRP alpha Recruitment of FYB to pSIRP alpha Recruitment of SCAP2 to pSIRP alpha SIRP gamma binds CD47 Interaction of DAP12 and SIRP beta SP-A/SP-D binds SIRP alpha Recruitment of Grb2 to pSIRP alpha PathwayStep4817 PathwayStep4816 PathwayStep4819 PathwayStep4818 PathwayStep4815 PathwayStep4823 PathwayStep4824 PathwayStep4820 PathwayStep4821 PathwayStep4822 Signal regulatory protein (SIRP) family interactions Authored: Garapati, P V, 2009-02-12 18:17:40 Edited: Garapati, P V, 2009-02-12 18:17:40 Pubmed11792697 Pubmed12023008 Pubmed16339511 Pubmed16691243 Pubmed19144521 Reactome Database ID Release 43391160 Reactome, http://www.reactome.org ReactomeREACT_23916 Reviewed: Barclay, AN, 2010-05-20 Signal regulatory protein (SIRP)alpha, also known as SHPS-1 or SIRPA or CD172a, is a transmembrane protein expressed mostly on myeloid cells. CD47, a widely expressed transmembrane protein, is a ligand for SIRP alpha, with the two proteins constituting a cell-cell communication system. The interaction of SIRP alpha with CD47 is important for the regulation of migration and phagocytosis. SIRP alpha functions as a docking protein to recruit and activate SHP-1 or SHP-2 at the cell membrane in response to extracellular stimuli. SIRP alpha also binds other intracellular proteins including the adaptor molecules Src kinase-associated protein (SKAP2 SKAP55hom/R), Fyn-binding protein/SLP-76-associated phosphoprotein (FYB/SLAP-130) and the tyrosine kinase PYK2. SIRP alpha also binds the extracellular proteins, surfactant-A (SP-A) and surfactant-D (SP-D). <br>In addition to SIRP alpha there are two closely related proteins in the SIRP family namely SIRP beta and SIRP gamma. These three family proteins show high sequence similarity and similar extracellular structural topology, including three Ig domains, but their ligand binding topology might differ. SIRP beta is expressed on myeloid cells, including monocytes, granulocytes and DCs. A natural ligand for SIRP beta remains unknown; SIRP gamma can bind to CD47 but the binding affinity is lower than that of SIRP alpha.