Laminin-322 degradation by MMP14

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R-HSA-3791155
Type
Reaction [transition]
Species
Homo sapiens
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Laminins are an important molecular component of the basement membranes (BMs) in a variety of tissue types. They have a cruciform shape, and are composed of three chains, alpha, beta and gamma., all of which have multiple subtypes. At the ultrastructural level, each laminin trimer appears as a cross-like structure with a large globular domain (LG domain) at the base of the cross. The LG domain is the C-terminal domain of the alpha subunit; it is divided into five homologous subdomains LG1-5 (Sugawara et al. 2008). Keratinocytes of the skin secrete numerous laminin isoforms, including laminin-511 and laminin-332.

Laminin-332 undergoes extensive proteolysis following secretion, which is essential for laminin-332 integration into the BM (Rousselle & Beck 2013). The 200 kDa alpha-3 subunit of laminin-332 is cleaved between the LG3-LG4 subdomains to generate a 165 kDa product. The 160 kDa gamma-2 subunit is cleaved at its N-terminus to produce a 105 kDa protein (Marinkovich et al. 1992). Tissue remodeling may lead to further proteolysis of the 105 kDa subunit within the N-terminus giving rise to a 80 kDa protein (Gianelli et al. 1997, Koshikawa et al. 2005). The resulting N-terminal fragment has EGF-like properties and may activate the EGF receptor, inducing cell migration (Schenk et al. 2003).

In much of the early literature it is not clear which subunit of the laminin trimer was cleaved, but in vitro studies have revealed specific enzymes involved in the processing of laminin-332 including MMP2, MMP14 (MT1-MMP), and the C-proteinase family of enzymes, especially bone morphogenic protein 1 (BMP1) and mammalian tolloid (mTLD), isoforms 1 and 3 respectively of UniProt P13497 BMP1 (Sugawara et al. 2008, Rousselle & Beck 2013).

The beta-3 and gamma-2 chains of laminin-322 are degraded by matrix metalloproteinase 14 (MMP14, MT1-MMP, Udayakumar et al. 2003, Koshikawa et al. 2000, 2005, Pirilä et al. 2003).

Literature References
PubMed ID Title Journal Year
12727852 Membrane type-1-matrix metalloproteinase expressed by prostate carcinoma cells cleaves human laminin-5 beta3 chain and induces cell migration

Udayakumar, TS, Chen, ML, Bair, EL, Von Bredow, DC, Cress, AE, Nagle, RB, Bowden, GT

Cancer Res. 2003
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Title
metalloendopeptidase activity of MMP14,TMPRSS6 [plasma membrane]
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