Sequence identity between the alpha 2-macroglobulin receptor and low density lipoprotein receptor-related protein suggests that this molecule is a multifunctional receptor.
Ten peptides, derived from human alpha 2-macroglobulin (alpha 2M) receptor by chemical or proteolytic digestion, were sequenced. Comparative analysis revealed that all of the resulting sequences were present within the cDNA-deduced structure of low density lipoprotein receptor-related protein (LRP) (Herz, J., Hamann, U., Rogne, S., Myklebost, O., Gausepohl, H., and Stanley, K. K. (1988) EMBO J. 7, 4119-4127). The findings provide evidence that the alpha 2M receptor and LRP are the same molecule. Further evidence comes from immunoprecipitation experiments using a monoclonal antibody specific for the alpha 2M receptor that show this molecule, like LRP, to contain two polypeptides of approximately 420 and 85 kDa that are noncovalently associated. An additional component of this receptor system is a 39-kDa polypeptide that co-purifies with the alpha 2M receptor during affinity chromatography. Solid phase binding studies reveal that the 39-kDa polypeptide binds with high affinity (Kd = 18 nM) to the 420-kDa component of the alpha 2M receptor. The apparent identity of LRP and the alpha 2M receptor suggests that this molecule is a multifunctional receptor with the capacity to bind diverse biological ligands and highlights a possible relationship between two previously unrelated biological processes, lipid metabolism and proteinase regulation.
Biochemistry Laboratory, American Red Cross, Rockville, Maryland 20855.
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Strickland
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Ashcom
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Williams
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Burgess
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Migliorini
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Argraves
D000595:Amino Acid Sequence; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008969:Molecular Sequence Data; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011971:Receptors, Immunologic / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D000511:alpha-Macroglobulins / Q000378:metabolism
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D000511:alpha-Macroglobulins