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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
42
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pubmed:dateCreated |
2002-10-15
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pubmed:abstractText |
KIM-1 (kidney injury molecule-1) is a type I transmembrane glycoprotein expressed on dedifferentiated renal proximal tubule epithelial cells undergoing regeneration after toxic or ischemic injury. The extracellular domain of KIM-1 is composed of an immunoglobulin-like domain topping a long mucin-like domain, a structure that points to a possible role in cell adhesion by homology to several known adhesion proteins. Two splice variants (a and b), of the human KIM-1 having identical extracellular domains, differ in their cytoplasmic domains and tissue distributions. In this study, we report that the KIM-1b transcript is expressed predominantly in adult human kidney. We describe the generation of 10 monoclonal antibodies against the extracellular domain of human KIM-1, the mapping of their binding sites, and their use in identifying various forms of the protein. We show that human KIM-1b is expressed in adult kidney cell lines, and we demonstrate that a soluble form of KIM-1 is shed constitutively into the culture medium of the cell lines expressing endogenous or recombinant KIM-1b by membrane-proximal cleavage. A monoclonal antibody that binds at or close to the proteolytic site can partially block the shedding of KIM-1. Release of soluble KIM-1 is enhanced by activating the cells with phorbol 12-myristate 13-acetate and can be inhibited with two metalloproteinase inhibitors, BB-94 (Batimastat) and GM6001 (Ilomastat), suggesting that the cleavage is mediated by a metalloproteinase. We propose that the shedding of KIM-1 in the kidney undergoing regeneration constitutes an active mechanism allowing dedifferentiated regenerating cells to scatter on denuded patches of the basement membrane and reconstitute a continuous epithelial layer.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Dipeptides,
http://linkedlifedata.com/resource/pubmed/chemical/GM 6001,
http://linkedlifedata.com/resource/pubmed/chemical/Havcr1protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylalanine,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thiophenes,
http://linkedlifedata.com/resource/pubmed/chemical/batimastat
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
39739-48
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pubmed:dateRevised |
2008-7-8
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pubmed:meshHeading |
pubmed-meshheading:12138159-Alternative Splicing,
pubmed-meshheading:12138159-Amino Acid Sequence,
pubmed-meshheading:12138159-Animals,
pubmed-meshheading:12138159-Antineoplastic Agents,
pubmed-meshheading:12138159-Binding Sites,
pubmed-meshheading:12138159-Biotinylation,
pubmed-meshheading:12138159-Blotting, Western,
pubmed-meshheading:12138159-COS Cells,
pubmed-meshheading:12138159-Cell Adhesion,
pubmed-meshheading:12138159-Cell Adhesion Molecules,
pubmed-meshheading:12138159-Cell Line,
pubmed-meshheading:12138159-Cell Membrane,
pubmed-meshheading:12138159-Cytoplasm,
pubmed-meshheading:12138159-Dipeptides,
pubmed-meshheading:12138159-Dose-Response Relationship, Drug,
pubmed-meshheading:12138159-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:12138159-Epithelial Cells,
pubmed-meshheading:12138159-Flow Cytometry,
pubmed-meshheading:12138159-Humans,
pubmed-meshheading:12138159-Kidney,
pubmed-meshheading:12138159-Membrane Proteins,
pubmed-meshheading:12138159-Metalloendopeptidases,
pubmed-meshheading:12138159-Microscopy, Fluorescence,
pubmed-meshheading:12138159-Molecular Sequence Data,
pubmed-meshheading:12138159-Phenylalanine,
pubmed-meshheading:12138159-Precipitin Tests,
pubmed-meshheading:12138159-Protease Inhibitors,
pubmed-meshheading:12138159-Protein Binding,
pubmed-meshheading:12138159-Protein Structure, Tertiary,
pubmed-meshheading:12138159-RNA, Messenger,
pubmed-meshheading:12138159-Recombinant Proteins,
pubmed-meshheading:12138159-Thiophenes,
pubmed-meshheading:12138159-Time Factors,
pubmed-meshheading:12138159-Tissue Distribution
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pubmed:year |
2002
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pubmed:articleTitle |
Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration.
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pubmed:affiliation |
BIOGEN Inc., Cambridge, Massachusetts 02142, USA. Veronique_Bailly@biogen.com
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pubmed:publicationType |
Journal Article
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