Abstract：
:The molecular interactions leading to organised, controlled extracellular matrix degradation are of central importance during growth, development and tissue repair, and when deregulated contribute to disease processes including cancer cell invasion. There are two major pathways for collagen degradation: one dependent on secreted and membrane-bound collagenases, the other on receptor-mediated collagen internalisation and intracellular processing. Despite the established importance of both pathways, the functional interaction between them is largely unknown. We demonstrate here, that the collagen internalisation receptor Endo180 (also known as CD280, uPARAP, MRC2) is a novel regulator of membrane-bound matrix metalloproteinase (MT1-MMP) activity, MT1-MMP-dependent MMP-2 activation and urokinase plasminogen activator (uPA) activity. We show close correlation between Endo180 expression, collagen accumulation and regulation of MT1-MMP cell-surface localisation and activity. We directly demonstrate, using collagen inhibition studies and non-collagen-binding mutants of Endo180, that the molecular mechanism underlying this regulation is the ability of Endo180 to bind and/or internalise collagens, rather than by acting as an interaction partner for pro-uPA and its receptor uPAR. These studies strongly support a functional interaction between two distinct collagen degradation pathways, define a novel mechanism regulating MT1-MMP activity and might have important implications for organised collagen clearance in the pericellular environment.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Messaritou G,East L,Roghi C,Isacke CM,Yarwood Hdoi
10.1242/jcs.044305subject
Has Abstractpub_date
2009-11-15 00:00:00pages
4042-8issue
Pt 22eissn
0021-9533issn
1477-9137pii
jcs.044305journal_volume
122pub_type
杂志文章abstract：:When human cells enter S-phase, overlapping differential inhibitory mechanisms downregulate the replication licensing factors ORC1, CDC6 and Cdt1. Such regulation prevents re-replication so that deregulation of any individual factor alone would not be expected to induce overt re-replication. However, this has been cha...
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journal_title：Journal of cell science
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abstract：:The monoclonal antibody Bx63 recognizes a centrosomal antigen of Drosophila melanogaster by indirect immunofluorescence and identifies two proteins, with apparent molecular weights of 185 x 10(3) and 66 x 10(3), on Western blots. We have used this antibody to isolate five clones (lambda cs1, -2, -3, -4 and lambda j63)...
journal_title：Journal of cell science
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journal_title：Journal of cell science
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更新日期：2007-01-01 00:00:00
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journal_title：Journal of cell science
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pub_type： 杂志文章,评审
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更新日期：2009-10-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-08-01 00:00:00
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journal_title：Journal of cell science
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doi：
更新日期：1995-09-01 00:00:00
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更新日期：2010-02-01 00:00:00
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journal_title：Journal of cell science
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doi：
更新日期：1992-02-01 00:00:00
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journal_title：Journal of cell science
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doi：
更新日期：1984-03-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章,收录出版
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更新日期：2006-01-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02650
更新日期：2005-11-15 00:00:00
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journal_title：Journal of cell science
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doi：
更新日期：2002-06-01 00:00:00
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更新日期：2010-06-01 00:00:00
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journal_title：Journal of cell science
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doi：
更新日期：1998-10-01 00:00:00
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journal_title：Journal of cell science
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更新日期：2001-10-01 00:00:00
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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更新日期：1993-07-01 00:00:00
