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* Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom; and
GlaxoSmithKline UK Ltd., Uxbridge, United Kingdom
Two closely related proteins, signal regulatory protein
(SIRP
; SHPS-1/CD172) and SIRP
, 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
and
genes and suggest that this gene should be termed SIRP
. We have expressed the extracellular region of SIRP
as a soluble protein and have shown that, like SIRP
, it binds CD47, but with a lower affinity (Kd,
23 µM) compared with SIRP
(Kd,
2 µM). mAbs specific to SIRP
show that it was not expressed on myeloid cells, in contrast to SIRP
and -
, being expressed instead on the majority of T cells and a proportion of B cells. The short cytoplasmic tail of SIRP
does not contain any known signaling motifs, nor does it contain a characteristic lysine, as with SIRP
, that is required for DAP12 interaction. DAP12 coexpression is a requirement for SIRP
surface expression, whereas SIRP
is expressed in its absence. The SIRP
-CD47 interaction may therefore not be capable of bidirectional signaling as with the SIRP
-CD47, but, instead, use unidirectional signaling via CD47 only.
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