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The low-density-lipoprotein receptor-related protein (LRP) is processed by furin in vivo and in vitro

Item Type:Article
Title:The low-density-lipoprotein receptor-related protein (LRP) is processed by furin in vivo and in vitro
Creators Name:Willnow, T.E. and Moehring, J.M. and Inocencio, N.M. and Moehring, T.J. and Herz, J.
Abstract:The low-density-lipoprotein receptor-related protein (LRP) is a multifunctional receptor involved in the clearance of a large number of diverse ligands, including proteases, protease-inhibitor complexes and lipoproteins. The mature receptor is composed of a 515 kDa and a 85 kDa subunit generated by proteolytic cleavage from a 600 kDa precursor polypeptide in a trans-Golgi compartment. Proteolytic processing occurs C-terminal to the tetrabasic amino acid sequence RHRR, a consensus recognition site for precursor processing endoproteases or convertases. In this study we have identified furin, a subtilisin-type protease, to be necessary for efficient processing of LRP in cells. Furin-deficient RPE.40 cells exhibited an impaired processing of endogenous LRP and of a recombinant soluble form of the receptor containing the processing site. The processing defect in RPE.40 cells could be complemented by expression of furin from a transfected cDNA in cultured cells and by purified furin in vitro. The impaired maturation of LRP in RPE.40 cells did not affect its intracellular transport, and correlated with a slight but consistent reduction in the endocytosis of LRP-specific ligands. These data suggest that proteolytic processing of LRP by furin is not necessary for intracellular trafficking but might be required for normal receptor activity.
Keywords:Amino Acid Sequence, Base Sequence, Binding Sites, CHO Cells, Complementary DNA, Furin, Iodine Radioisotopes, LDL-Receptor Related Protein 1, Molecular Sequence Data, Post-Translational Protein Processing, Immunologic Receptors, Sensitivity and Specificity, Subtilisins, Tissue Plasminogen Activator, Transfection, Animals, Mice, Cricetinae
Source:Biochemical Journal
ISSN:0264-6021
Publisher:Portland Press
Volume:313
Number:Pt 1
Page Range:71-76
Date:1 January 1996
Additional Information:The final version of record is available at http://www.biochemj.org/bj/313/0071/bj3130071.htm
Official Publication:http://www.biochemj.org/bj/313/0071/bj3130071.htm
PubMed:View item in PubMed

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