层粘连蛋白-332通过层粘连蛋白-322降解细胞外蛋白酶降解

稳定的标识符
R-HSA-1566979
类型
反应[过渡]
物种
HOMO SAPIENS.
舱室
路径的位置
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层粘连蛋白-332通过层粘连蛋白-322降解细胞外蛋白酶降解
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层链是基底膜(BMS)的各种组织类型的重要分子量。它们具有十字形的形状,并且由三个链,α,β和伽马组成。所有这些都有多个亚型。在超微结构水平,每个层粘素三聚体在交叉的底部时显示为具有大的球形结构域(LG域)的交叉结构。LG域是Alpha亚基的C末端域;它分为五个同源亚域LG1-5(Sugawara等,2008)。皮肤的角质形成细胞分泌着许多层内同种型,包括层粘连蛋白-511和层粘连蛋白-332。Laminin-332在分泌后经历了广泛的蛋白水解,这对于Laminin-332集成到BM(Rousselle&Beck 2013)至关重要。层粘连蛋白-332的200kDaα-3亚基在LG3-LG4亚域之间切割以产生165kDa产物。160kDaγ-2亚基在其N-末端切割以产生105kDa蛋白(Marinkovich等人1992)。组织重塑可能导致N-末端内的105kDa亚基的进一步蛋白水解,从而产生80kDa蛋白(Gianelli等,1997,Koshikawa等,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). Many proteases have been demonstrated to degrade specific subunits of laminin-332. The beta-3 chain is degraded by matrix metalloproteinase 14 (MMP14, MT1-MMP, Udayakumar et al. 2003) and MMP7 (Remy et al. 2006). The alpha-3 chain is degraded by plasmin (Goldfinger et al. 1998, 1999) and BMP1 (and its isoform mTLD, Veitch et al. 2003). Laminin gamma-2 chain is degraded by MMP14 (Koshikawa et al. 2000, 2005, Pirilä et al. 2003) , MMP2 (Gianelli et al. 1997, Pirilä et al. 2003), MMP3, 12, 13 (Pirilä et al. 2003), 19 (Sadowski et al. 2005), MMP20 (Väänänen et al. 2001, Pirilä et al. 2003), BMP1 (Amano et al. 2000, Kessler et al. 2001) and mTLD (Veitch et al. 2003). Plasmin cleavage of laminin-111 yields fragments with sizes that correspond to the cleavage of the alpha and beta/gamma components (Gutiérrez-Fernández et al. 2009). In this reaction laminin-322 is represented with all 3 component peptides cleaved.

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丝氨酸型内肽酶活性,层粘连蛋白-332降解细胞外蛋白酶[细胞外区域]

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