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J. Biol. Chem., Vol. 265, Issue 29, 17401-17404, 10, 1990
DK Strickland, JD Ashcom, S Williams, WH Burgess, M Migliorini and WS Argraves
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.
Sequence identity between the alpha 2-macroglobulin receptor and low density lipoprotein receptor-related protein suggests that this molecule is a multifunctional receptor
Biochemistry Laboratory, American Red Cross, Rockville, Maryland 20855.
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