Reactome | Signal regulatory protein family interactions

Signal regulatory protein family interactions

Stable Identifier

R-HSA-391160

DOI

10.3180/REACT_23752.1

Type

Pathway

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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Signal regulatory protein family interactions

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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
16339511	A nomenclature for signal regulatory protein family members Liu, Y, Howard, CJ, Parkos, CA, van den Berg, TK, van Beek, EM, Vignery, A, Neel, BG, Barclay, AN, Wright, M, Vivier, E, Buhring, HJ, Kasuga, M, Hamaguchi, M, Colonna, M, Matozaki, T, Zawatzky, R, Sano, S	J Immunol	2005
16691243	The SIRP family of receptors and immune regulation Barclay, AN, Brown, MH	Nat Rev Immunol	2006
12023008	SHPS-1, a multifunctional transmembrane glycoprotein Ruhul Amin, AR, Matsuda, S, Oshima, K, Hamaguchi, M, Suzuki, A	FEBS Lett	2002
19144521	Functions and molecular mechanisms of the CD47-SIRPalpha signalling pathway Ohnishi, H, Okazawa, H, Matozaki, T, Murata, Y	Trends Cell Biol	2009
11792697	Signal regulatory protein (SIRPalpha), a cellular ligand for CD47, regulates neutrophil transmigration Parkos, CA, Liu, Y, Buhring, HJ, Zen, K, Schnell, FJ, Burst, SL, Williams, IR	J Biol Chem	2002