The EGF-TM7 family: unusual structures at the leukocyte surface

The isolation of cDNA clones encoding mouse F4/80, human epidermal growth factor (EGF) module-containing mucin-like hormone receptor 1 (EMR1) and human CD97 has resulted in the description of a novel family of seven-transmembrane spanning cell surface molecules. These members of the EGF-TM7 family are characterized by a variable number of NH2-terminal EGF domains and seven transmembrane-spanning hydrophobic regions, which demonstrate a degree of sequence homology to the corresponding region in members of the G-protein-coupled peptide hormone receptor family. The F4/80 molecule is macrophage-restricted, as determined by immunohistochemical analysis of a wide range mouse tissues, while mRNA transcripts encoding EMR1, the predicted human F4/80 homologue, also appear to be abundantly expressed by cells of the myelomonocytic lineage. CD97, for which a cellular ligand has been identified (CD55), is expressed on a diverse array of leukocytes and is markedly upregulated on activated T and B cells. The regulation of expression of the EGF-TM7 genes, the physiologic function(s) of these novel receptors and the further identification of their ligands is the subject of both intense study and this review.