Document Detail


Shedding of kidney injury molecule-1 by membrane-type 1 matrix metalloproteinase.
MedLine Citation:
PMID:  22843853     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Co-expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) with kidney injury molecule-1 (KIM-1) in HEK293T cells resulted in cleavage and shedding of KIM-1 ectodomain. Analysis of cleavage products using KIM-1 mutants localized cleavage site at the juxtamembrane region. HT1080 cells were stably transfected with expression plasmid for KIM-1 or its mutant with deletion of the juxtamembrane region (Asp(261)-Gly(295)) to establish HT/KIM-1 or HT/ΔKIM-1 cells, respectively. KIM-1 protein appeared on cell surface at low level in HT/KIM-1 cells, and accumulated by the treatment with MMP inhibitor BB-94 or small interfering RNA (siRNA) to MT1-MMP, indicating that MT1-MMP is involved in cleavage and shedding of KIM-1. In contrast, HT/ΔKIM-1 cells expressed KIM-1 protein at high level regardless of BB-94 or siRNA treatment. Cells expressing high level KIM-1 protein exhibited phagocytosis of Escherichia coli and reduced cell adhesion and spreading on collagen-coated plate compared with KIM-1 negative cells. Control HT1080 and HT/KIM-1 cells showed significantly higher invasive growth in collagen gel, cell migration on collagen-coated plate and liver metastasis in chick embryo than HT/ΔKIM-1 cells. These results suggest that KIM-1 negatively regulates cellular function mediated through interaction with collagen, and MT1-MMP abrogates it through the cleavage and shedding of KIM-1.
Authors:
Luyang Guo; Takahisa Takino; Yoshio Endo; Takahiro Domoto; Hiroshi Sato
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-26
Journal Detail:
Title:  Journal of biochemistry     Volume:  -     ISSN:  1756-2651     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376600     Medline TA:  J Biochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, 920-1192 Shedding of KIM-1 by MT1-MMP.
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