Signal regulatory protein family interactions

Stable Identifier
R-HSA-391160
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Homo sapiens
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Signal regulatory protein alpha (SIRPA, SHPS1, 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 SIRPA with CD47 is important for the regulation of migration and phagocytosis. SIRPA functions as a docking protein to recruit and activate PTPN6 (SHP-1) or PTPN11 (SHP-2) at the cell membrane in response to extracellular stimuli. SIRPA 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. SIRPA also binds the extracellular proteins, surfactant-A (SP-A) and surfactant-D (SP-D).
The SIRP family members SIRPB and SIRPG show high sequence similarity and similar extracellular structural topology, including three Ig domains, but their ligand binding topology might differ. SIRPB is expressed on myeloid cells, including monocytes, granulocytes and DCs. It has no known natural ligand. SIRPG can bind CD47 but with lower affinity than SIRPA.

Literature References
PubMed ID Title Journal Year
16691243 The SIRP family of receptors and immune regulation

Barclay, AN, Brown, MH

Nat Rev Immunol 2006
16339511 A nomenclature for signal regulatory protein family members

van den Berg, TK, van Beek, EM, Buhring, HJ, Colonna, M, Hamaguchi, M, Howard, CJ, Kasuga, M, Liu, Y, Matozaki, T, Neel, BG, Parkos, CA, Sano, S, Vignery, A, Vivier, E, Wright, M, Zawatzky, R, Barclay, AN

J Immunol 2005
12023008 SHPS-1, a multifunctional transmembrane glycoprotein

Oshima, K, Ruhul Amin, AR, Suzuki, A, Hamaguchi, M, Matsuda, S

FEBS Lett 2002
19144521 Functions and molecular mechanisms of the CD47-SIRPalpha signalling pathway

Matozaki, T, Murata, Y, Okazawa, H, Ohnishi, H

Trends Cell Biol 2009
11792697 Signal regulatory protein (SIRPalpha), a cellular ligand for CD47, regulates neutrophil transmigration

Liu, Y, Buhring, HJ, Zen, K, Burst, SL, Schnell, FJ, Williams, IR, Parkos, CA

J Biol Chem 2002
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