title: Shedding of kidney injury molecule-1 by membrane-type 1 matrix metalloproteinase.
abstract: 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: Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors: Luyang
authors: L
authors: Guo
authors: Takahisa
authors: T
authors: Takino
authors: Yoshio
authors: Y
authors: Endo
authors: Takahiro
authors: T
authors: Domoto
authors: Hiroshi
authors: H
authors: Sato
mesh_terms: D002478:Cells, Cultured; D057809:HEK293 Cells; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D011991:Receptors, Virus / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000494:pharmacology
chemical_list: C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D011991:Receptors, Virus; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D053511:Matrix Metalloproteinase 14