Document Detail


Cleavage of parathyroid hormone in macrophage endosomes illustrates a novel pathway for intracellular processing of proteins.
MedLine Citation:
PMID:  2760027     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Most ligands which are taken up by macrophages are transported to lysosomes where they are degraded to their constituents by a concert of acid hydrolases. This process requires a number of intracellular events which result in the transport of ligands from light density endosomes to the more dense lysosomes. In contrast, our studies have shown that macrophages may process some incoming ligands in endosomes (Diment, S., and Stahl, P. D. (1985) J. Biol. Chem. 260, 15311-15317) and that cathepsin D, an aspartyl protease, is localized in these organelles (Diment, S., Leech, M. S., and Stahl, P. D. (1988) J. Biol. Chem. 263, 6901-6907). Using rabbit alveolar macrophages, which can be subjected to subcellular fractionation, we have traced the intracellular transport and processing of bovine parathyroid hormone (PTH-(1-84]. We present evidence that macrophages internalize PTH-(1-84). Once in endosomes the hormone is cleaved to fragments which include a bioactive peptide, PTH-(1-34), and then the fragments are returned to the extracellular medium, without delivery to lysosomes. The entire cycle from initial binding to release of PTH-(1-34) is achieved within 10-15 min, a time period consistent with findings in vivo. Our data provide evidence for a novel route for processing of an endocytosed ligand.
Authors:
S Diment; K J Martin; P D Stahl
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  264     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1989 Aug 
Date Detail:
Created Date:  1989-09-11     Completed Date:  1989-09-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  13403-6     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, Washington University School of Medicine, St. Louis Missouri.
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MeSH Terms
Descriptor/Qualifier:
Animals
Endocytosis
Kinetics
Macrophages / metabolism*
Organoids / metabolism*
Parathyroid Hormone / genetics*,  metabolism
Protein Processing, Post-Translational*
Rabbits
Subcellular Fractions / metabolism
Grant Support
ID/Acronym/Agency:
AI 20015/AI/NIAID NIH HHS; CA 12858/CA/NCI NIH HHS; DK 09976/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Parathyroid Hormone

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