THE HUMAN ALPHA-2-MACROGLOBULIN RECEPTOR - IDENTIFICATION OF A 420-KD CELL-SURFACE GLYCOPROTEIN SPECIFIC FOR THE ACTIVATED CONFORMATION OF ALPHA-2-MACROGLOBULIN

Ligand affinity chromatography was used to purify a cell surface α2-macroglobulin (α2M) receptor. Detergent extracts of human placenta were applied to an affinity matrix consisting of α2M, previously reacted with methylamine, coupled to Sepharose. Elution with EDTA specifically released polypeptides with apparent molecular masses of 420 and 39 kD. In some preparations, small amounts of a 90-kD polypeptide were observed. The 420- and 39-kD polypeptides appear specific for the forms of α2M activated by reaction with proteinases or methylamine and do not bind to an affinity matrix consisting of native α2M coupled to Sepharose. Separation of these two polypeptides was accomplished by anion exchange chromatography, and binding activity was exclusively associated with the 420-kD polypeptide. The purified 420-kD protein binds to the conformationally altered forms of α2M that are known to specifically interact with α2M receptors and does not bind to native α2M. Binding of the 420-kD polypeptide to immobilized wheat germ agglutinin indicates that this polypeptide is a glycoprotein. The cell surface localization of the 420-kD glycoprotein was confirmed by affinity chromatography of extracts from surface radioiodinated fibroblasts. These properties suggest that the 420-kD polypeptide is a cell surface receptor for the activated forms of α2M.