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PMID: 8546712 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Biochemical journal ·Vol. 313 ( Pt 1) ·1996-01-01 ·Pages 71-6

Willnow TE, Moehring JM, Inocencio NM, Moehring TJ, 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.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Binding Sites CHO Cells/metabolism Cricetinae DNA, Complementary/genetics Furin Iodine Radioisotopes Low Density Lipoprotein Receptor-Related Protein-1 Mice Molecular Sequence Data Protein Processing, Post-Translational Receptors, Immunologic/metabolism Sensitivity and Specificity Subtilisins/genetics,metabolism Tissue Plasminogen Activator/pharmacokinetics Transfection
Chemicals
DNA, Complementary Iodine Radioisotopes Low Density Lipoprotein Receptor-Related Protein-1 Receptors, Immunologic Subtilisins Tissue Plasminogen Activator Furin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Willnow T E
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Moehring J M
Inocencio N M
Moehring T J
Herz J
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj3130071
Published
1996-01-01
Pages
71-6
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1216911
Subset
IM
Grants
NIAID NIH HHS · AI09100 · United States
NHLBI NIH HHS · HL 20948 · United States
External Links
PubMed source DOI: 10.1042/bj3130071 PMC Full Text View journal details
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