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Low density lipoprotein receptor related protein (LRP): A multiligand receptor
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PLENARY 3
227 LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN (LRP): A MULTILIGAND RECEPTOR Dudley K. Strickland, Maria Z. Kounnas, Suzanne E. Williams, and W. Scott Argraves. American Red Cross, Rockville MD 20855. LRP is a large cell surface receptor with a 5 15 kDa heavy chain which contains the ligand binding domains, and an 85 kDa light chain which contains the transmembrane and cytoplasmic domain. These two subunits are noncovalently associated on the cell surface. LRP, a member of the LDL receptor family, is widely expressed by many types of cells, including hepatocytes, fibroblasts, macrophages, and neurons. A 39 kDa protein, termed the receptor associated protein (RAP), binds with high affinity to multiple independent sites on LRP and antagonizes the binding of ligands to this receptor. Although the biological role of RAP is not completely understood, it may function
to modulate ligand binding by LRP. LRP binds numerous ligands, and appears responsible for mediating the removal of proteinases, proteinase-inhibitor complexes, and certain apoE- and lipoprotein lipase-enriched lipoproteins. Some of these ligands include azmacroglobulin-proteinase complexes, complexes of tissue type (tPA) and urinary-type (uPA) plasminogen activator with plasminogen activator inhibitor type I. Interestingly, LRP also binds and internalizes certain proteinases, such as tPA and UPA, and thus it is likely that LRP plays a major role in the hepatic removal of these two proteinases from the plasma. The ability of LRP to bind and rapidly internalize both proteinases and proteinase-inhibitor complexes suggests a major role for this receptor in regulating proteinase activity.
PLENARY 3
227 LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN (LRP): A MULTILIGAND RECEPTOR Dudley K. Strickland, Maria Z. Kounnas, Suzanne E. Williams, and W. Scott Argraves. American Red Cross, Rockville MD 20855. LRP is a large cell surface receptor with a 5 15 kDa heavy chain which contains the ligand binding domains, and an 85 kDa light chain which contains the transmembrane and cytoplasmic domain. These two subunits are noncovalently associated on the cell surface. LRP, a member of the LDL receptor family, is widely expressed by many types of cells, including hepatocytes, fibroblasts, macrophages, and neurons. A 39 kDa protein, termed the receptor associated protein (RAP), binds with high affinity to multiple independent sites on LRP and antagonizes the binding of ligands to this receptor. Although the biological role of RAP is not completely understood, it may function
to modulate ligand binding by LRP. LRP binds numerous ligands, and appears responsible for mediating the removal of proteinases, proteinase-inhibitor complexes, and certain apoE- and lipoprotein lipase-enriched lipoproteins. Some of these ligands include azmacroglobulin-proteinase complexes, complexes of tissue type (tPA) and urinary-type (uPA) plasminogen activator with plasminogen activator inhibitor type I. Interestingly, LRP also binds and internalizes certain proteinases, such as tPA and UPA, and thus it is likely that LRP plays a major role in the hepatic removal of these two proteinases from the plasma. The ability of LRP to bind and rapidly internalize both proteinases and proteinase-inhibitor complexes suggests a major role for this receptor in regulating proteinase activity.