Proteolytic processing of laminin‐5 by MT1‐MMP in tissues and its effects on epithelial cell morphology

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Abstract
SPECIFIC AIMSWe aimed to define MT1-MMP cleavage sites on Ln-5 in detail; define the correlation between MT1-MMP cleavage of Ln-5 and epithelial cell differentiation; and determine whether MT1-MMP is the physiological proteolytic enzyme for Ln-5 in vivo by analyzing tissues from MT1-MMP KO mice.PRINCIPAL FINDINGS1. Identification of MT1-MMP cleavage sites on rat Ln-5 γ2 chainOur previous data demonstrate that MMP2 cleaves Ln-5 γ2 chain at the boundary of domain III (DIII) with DII, generating a 80 kDa γ2x chain (γ2→γ2x). We proposed that MT1-MMP used this MMP-2 cleavage site and the conserved γ2→γ2′ site located at the boundary of DIII and DIV domains, giving rise to the 100 kDa γ2′ chain.Such a proposal is of interest because MMP cleavage simultaneously at both sites (γ2→γ2x and γ2→γ2′) excises the DIII domain, which has an EGF-like structure. Therefore, we characterized in detail the exact positions of the MT1-MMP cleavage sites on γ2, especially the one that generates γ2′ (γ2→γ2′). We produced a recomb...
Funding Information
  • National Institutes of Health (GM46902, CA47858)