title: Dual regulation of SIRPalpha phosphorylation by integrins and CD47.
abstract: Signal regulatory protein alpha (SIRPalpha, SHPS-1) is a plasma membrane receptor for CD47 and a key regulator of phagocytosis, growth factor signaling, and migration. Phosphorylation of immunoreceptor tyrosine-based inhibition motifs in its cytoplasmic tail is essential for the functional effects of SIRPalpha, at least in part, because the phosphorylated immunoreceptor tyrosine-based inhibition motifs recruit Src homology 2 domain-containing tyrosine phosphatases. Ligation by CD47 and integrin engagement both have been thought to regulate SIRPalpha phosphorylation. However, their distinct contributions have not been distinguished. Here, we show that the importance of CD47 varies with cell type, since ligation of CD47 is not necessary for SIRPalpha phosphorylation in myeloid cells, whereas it is required in endothelial cells. In contrast, integrin-mediated adhesion is required for SIRPalpha phosphorylation in both cell types. This shows that SIRPalpha phosphorylation is dually regulated and demonstrates a new mechanism for functional cooperation between integrins and the integrin-associated protein CD47.
authors.affiliation: Program in Microbial Pathogenesis and Host Defense, Genentech Hall, University of California, San Francisco, California 94158, USA.
authors.forename: Mette L
authors.initials: ML
authors.lastname: Johansen
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Brown
mesh_terms: D000818:Animals; D051928:CD47 Antigen / Q000378:metabolism*; D002448:Cell Adhesion; D042783:Endothelial Cells; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D022423:Myeloid Cells; D010766:Phosphorylation; D011971:Receptors, Immunologic / Q000378:metabolism*
chemical_list: D051928:CD47 Antigen; D016023:Integrins; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic