Human Lymphocytes Interact Directly with CD47 through a Novel Member of the Signal Regulatory Protein (SIRP) Family

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 uni...

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Veröffentlicht in:The Journal of immunology (1950) 2004-08, Vol.173 (4), p.2562-2570
Hauptverfasser: Brooke, Gary, Holbrook, Joanna D, Brown, Marion H, Barclay, A. Neil
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creator Brooke, Gary
Holbrook, Joanna D
Brown, Marion H
Barclay, A. Neil
description 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.
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subjects Adaptor Proteins, Signal Transducing
Amino Acid Sequence
Animals
Antibodies, Monoclonal
Antibody Specificity
Antigens, CD - immunology
Antigens, CD - metabolism
Antigens, Differentiation - chemistry
Antigens, Differentiation - physiology
Apoptosis - immunology
CD47 Antigen
Cells, Cultured
Cloning, Molecular
Flow Cytometry
Humans
Jurkat Cells
Lymphocytes - immunology
Membrane Glycoproteins - chemistry
Membrane Glycoproteins - physiology
Membrane Proteins
Molecular Sequence Data
Neural Cell Adhesion Molecule L1 - chemistry
Neural Cell Adhesion Molecule L1 - physiology
Polymerase Chain Reaction
Precipitin Tests
Receptors, Immunologic - chemistry
Receptors, Immunologic - immunology
Receptors, Immunologic - physiology
Surface Plasmon Resonance
U937 Cells
title Human Lymphocytes Interact Directly with CD47 through a Novel Member of the Signal Regulatory Protein (SIRP) Family
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