Signal-regulatory protein is selectively expressed by myeloid and neuronal cells.
Signal-regulatory proteins (SIRP) are transmembrane glycoproteins with three extracellular Ig-like domains, closely related to Ag receptors Ig, TCR, and MHC, and a cytoplasmic domain with two immunoreceptor with tyrosine-based inhibition motifs that can interact with src homology 2 domain-containing phosphatases. SIRP have previously been shown to inhibit signaling through receptor tyrosine kinases, but their physiologic function is unknown. Here we demonstrate by expression cloning that the mAbs ED9, ED17, and MRC-OX41 recognize rat SIRP. In addition, we show for the first time that rat SIRP is selectively expressed by myeloid cells (macrophages, monocytes, granulocytes, dendritic cells) and neurons. Moreover, SIRP ligation induces nitric oxide production by macrophages. This implicates SIRP as a putative recognition/signaling receptor in both immune and nervous systems.
Cell Adhesion Laboratory, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom.
S
S
Adams
L J
LJ
van der Laan
E
E
Vernon-Wilson
C
C
Renardel de Lavalette
E A
EA
Döpp
C D
CD
Dijkstra
D L
DL
Simmons
T K
TK
van den Berg
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000943:Antigens, Differentiation; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D003713:Dendritic Cells / Q000378:metabolism*; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D010586:Phagocytes / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D011971:Receptors, Immunologic; D009569:Nitric Oxide