| Protease nexins: cell-secreted proteins that mediate the binding, internalization, and degradation of regulatory serine proteases. | |
| | |
MedLine Citation:
|
PMID: 6317700 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The protease nexins (PN-I, Mr approximately 38,000; PN-II, Mr approximately 95,000; and PN-III, Mr approximately 31,000) are recently described cell-secreted proteins that selectively link to regulatory serine proteases in the extracellular environment and mediate their cellular binding, internalization, and degradation. In the present studies we compared the protease nexins with respect to protease specificity, heparin sensitivity, and general mode of action. By competitive binding assays using [125I]-thrombin, [125I]-nerve growth factor-gamma (125I-NGF-gamma), and [125I]-epidermal growth factor binding protein (125I-EGF-binding protein), we characterized the nexins in terms of protease specificity and determined that PN-I links to and mediates the cellular binding of thrombin or urokinase, whereas PN-II and PN-III preferentially link to and mediate the cellular binding of the EGF binding protein and NGF-gamma, respectively. In addition, whereas the ability of PN-I to link to thrombin is strongly modulated by heparin, PN-II and PN-III are essentially unaffected by heparin. The linkage of each of the nexins to their respective proteases requires the catalytic site serine of the protease, judged by the inability of diisopropylphospho (DIP) derivatives of the proteases tested to link to their respective nexins. Subsequent to linkage, the nexin:protease complexes are bound to cells, rapidly internalized, and ultimately degraded via a monensin-sensitive apparently lysosomal pathway, although each nexin:protease complex is degraded at its own characteristic rate. Importantly, the protease nexins provide the major pathway through which human fibroblasts interact with each of the serine proteases studied. Taken together, these data suggest that the nexins are a unique class of cell-secreted proteins that enable cells to monitor and selectively regulate specific serine proteases in their environment. |
| | |
Authors:
|
D J Knauer; J A Thompson; D D Cunningham |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Journal of cellular physiology Volume: 117 ISSN: 0021-9541 ISO Abbreviation: J. Cell. Physiol. Publication Date: 1983 Dec |
Date Detail:
|
Created Date: 1984-02-14 Completed Date: 1984-02-14 Revised Date: 2009-11-19 |
Medline Journal Info:
|
Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 385-96 Citation Subset: IM |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amyloid beta-Protein Precursor Binding Sites Carrier Proteins / metabolism, physiology* Cell Membrane / enzymology* Cells, Cultured Endocytosis Endopeptidases / metabolism* Fibroblasts Heparin / pharmacology Humans Lysosomes / enzymology Male Monensin / pharmacology Nerve Growth Factors / metabolism Receptor, Epidermal Growth Factor Receptors, Cell Surface / metabolism Serine Endopeptidases Thrombin / metabolism Urokinase-Type Plasminogen Activator / metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
CA 09054/CA/NCI NIH HHS; CA 12306/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Amyloid beta-Protein Precursor; 0/Carrier Proteins; 0/Nerve Growth Factors; 0/Receptors, Cell Surface; 0/protease nexins; 17090-79-8/Monensin; 9005-49-6/Heparin; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 3.4.-/Endopeptidases; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.5/Thrombin; EC 3.4.21.73/Urokinase-Type Plasminogen Activator |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Immunofluorescent visualization of specifically bound thrombin reveals cellular heterogeneity in num...
Next Document: A reevaluation of the response of human umbilical vein endothelial cells to certain growth factors.