CD97 IS A PROCESSED, 7-TRANSMEMBRANE, HETERODIMERIC RECEPTOR-ASSOCIATED WITH INFLAMMATION

CD97 is a receptor that spans the membrane seven times, a defining fea ture of C protein-coupled receptors, CD97 is predominantly expressed i n 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 C protein-coupled receptors characterized to date of b eing processed intracellularly in either the endoplasmic reticulum or early Golgi from a proprotein into a noncovalently associated two-subu nit structure that becomes expressed on the cell surface and is compos ed of a large extracellular protein (CD97 alpha) and a seven-membrane spanning protein (CD97 beta), CD97 beta is part of an evolutionarily c onserved subfamily of four proteins, including two Caenorhabditis eleg ans proteins of as yet unknown function, which is distinct from but mo st closely related to the glucagon receptor family, CD97 alpha exists in three alternatively spliced isoforms that contain between three and five epidermal growth factor (EGF)-like repeats that are related to t he calcium binding EGF-like repeats in the microfibril protein fibrill in, Leukocytes strongly positive for CD97 are concentrated at sites of inflammation relative to CD97 expression in normal lymphoid tissues, Soluble CD97 alpha was found in body fluids from inflamed tissues, sug gesting that a functional consequence of the CD97 heterodimeric struct ure is the stable existence of CD97 alpha in a cellfree form, CD97 app ears to be a multifunctional protein that may play a signal transducti on role associated with the establishment or development of an inflamm atory process.