CD97 is a processed, seven-transmembrane, heterodimeric receptor associated with inflammation.
CD97 is a receptor that spans the membrane seven times, a defining feature of G protein-coupled receptors. CD97 is predominantly expressed in leukocytes, but the function and accurate protein structure of this receptor have not been described. We show here that CD97 has the novel property among G protein-coupled receptors characterized to date of being processed intracellularly in either the endoplasmic reticulum or early Golgi from a proprotein into a noncovalently associated two-subunit structure that becomes expressed on the cell surface and is composed of a large extracellular protein (CD97alpha) and a seven-membrane spanning protein (CD97beta). CD97beta is part of an evolutionarily conserved subfamily of four proteins, including two Caenorhabditis elegans proteins of as yet unknown function, which is distinct from but most closely related to the glucagon receptor family. CD97alpha exists in three alternatively spliced isoforms that contain between three and five epidermal growth factor (EGF)-like repeats that are related to the calcium binding EGF-like repeats in the microfibril protein fibrillin. Leukocytes strongly positive for CD97 are concentrated at sites of inflammation relative to CD97 expression in normal lymphoid tissues. Soluble CD97alpha was found in body fluids from inflamed tissues, suggesting that a functional consequence of the CD97 heterodimeric structure is the stable existence of CD97alpha in a cellfree form. CD97 appears to be a multifunctional protein that may play a signal transduction role associated with the establishment or development of an inflammatory process.
Gray
J X
JX
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Haino
M
M
Roth
M J
MJ
Maguire
J E
JE
Jensen
P N
PN
Yarme
A
A
Stetler-Stevenson
M A
MA
Siebenlist
U
U
Kelly
K
K
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D015703:Antigens, CD; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004815:Epidermal Growth Factor / Q000737:chemistry; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D043562:Receptors, G-Protein-Coupled; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000276:immunology
C095004:ADGRE5 protein, human; D015703:Antigens, CD; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D004815:Epidermal Growth Factor