Human lymphocytes interact directly with CD47 through a novel member of the signal regulatory protein (SIRP) family.

Journal article

Two closely related proteins, signal regulatory protein alpha (SIRPalpha; SHPS-1/CD172) and SIRPbeta, have been described in humans. The existence of a third SIRP protein has been suggested by cDNA sequence only. We show that this third SIRP is a separate gene that is expressed as a protein with unique characteristics from both alpha and beta genes and suggest that this gene should be termed SIRPgamma. We have expressed the extracellular region of SIRPgamma as a soluble protein and have shown that, like SIRPalpha, it binds CD47, but with a lower affinity (K(d), approximately 23 microM) compared with SIRPalpha (K(d), approximately 2 microM). mAbs specific to SIRPgamma show that it was not expressed on myeloid cells, in contrast to SIRPalpha and -beta, being expressed instead on the majority of T cells and a proportion of B cells. The short cytoplasmic tail of SIRPgamma does not contain any known signaling motifs, nor does it contain a characteristic lysine, as with SIRPbeta, that is required for DAP12 interaction. DAP12 coexpression is a requirement for SIRPbeta surface expression, whereas SIRPgamma is expressed in its absence. The SIRPgamma-CD47 interaction may therefore not be capable of bidirectional signaling as with the SIRPalpha-CD47, but, instead, use unidirectional signaling via CD47 only.

Authors: Brooke, G; Holbrook, J; Brown, M; Barclay, N

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 173
• Issue: 4
• Pages: 2562-2570
• Publication date: 2004-08-01
• DOI: 10.4049/jimmunol.173.4.2562
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Membrane Proteins; Antigens, CD; Adaptor Proteins, Signal Transducing; Animals; U937 Cells; Antibody Specificity; Amino Acid Sequence; Neural Cell Adhesion Molecule L1; Membrane Glycoproteins; Antibodies, Monoclonal; Surface Plasmon Resonance; Polymerase Chain Reaction; Molecular Sequence Data; Flow Cytometry; Antigens, CD47; Jurkat Cells; Precipitin Tests; Cells, Cultured; Cloning, Molecular; Antigens, Differentiation; Humans; Receptors, Immunologic; Lymphocytes; Apoptosis