The mouse matrix metalloproteinase, epilysin (MMP-28), is alternatively spliced and processed by a furin-like proprotein convertase

Abstract

Epilysin (MMP-28) is a recently identified member of the matrix metalloproteinase (MMP) family. To explore the expression of epilysin in vivo and to gain insight into its biological functions, we have cloned the mouse epilysin cDNA and determined its expression. The amino acid sequence of the mouse protein is 85% identical with the human sequence and contains conserved features such as an RKKR furin-activation sequence following the prodomain. Unexpectedly, we found two alternatively spliced forms of the epilysin mRNA lacking 30 and 72 nt at the beginning of the seventh exon coding for part of the haemopexin domain. Expression of recombinant epilysin in HT-1080 fibrosarcoma cells indicated that epilysin was secreted as a major 48 kDa form and a minor 58 kDa form. Expression of the 58 kDa form was increased by a synthetic furin inhibitor at the expense of the 48 kDa form, suggesting that furin cleaves and activates epilysin. Epilysin mRNA was detected in a number of mouse tissues, with the highest expression in the lung, placenta, heart and uterus, and lower levels in the testis and gastrointestinal tract. The wide expression of epilysin in intact, healthy tissues suggests that this MMP functions in physiological tissue homoeostasis and turnover.

Control of matrix metalloproteinase catalytic activity

“…1). Furin is a type 1 membrane, subtilisin-like serine protease present in the trans-Golgi network (Thomas, 2002), and thus, MMPs with a furin cleavage site are processed intracellularly before secretion (Illman et al, 2003;Kang et al, 2002;Pei and Weiss, 1995;Sato et al, 1996). For the other MMPs, the mode of activation is more presumed than proved, and the in vivo mechanism for activation of most non-furin cleaved proMMPs is unknown.…”

Thyroid hormone induces myocardial matrix degradation by activating matrix metalloproteinase-1

“…Degradation of matrix proteins is caused by matrix metalloproteinases (MMPs), which belongs to a family of proteolytic enzymes (Shapiro, 1998). The family of MMPs consists of more than 20 different zinc-containing Ca 2+ -dependent endopeptidases which cause proteolysis of different kinds of matrix proteins including collagens, gelatins, fibronectin and laminins (Spinale et al, 2000;Creemers et al, 2001;Illman et al, 2003). In mammalian myocardium, MMP-1 has been demonstrated to play an important role in the degradation of interstitial collagens (Spinale, 2002).…”

Neural MMP‐28 expression precedes myelination during development and peripheral nerve repair

“…For example, MMP-28 is detected in the embryonic heart and skin, both tissues that have been shown to express MMP-28 Marchenko and Strongin, 2001;Illman et al, 2003). In the skin, MMP-28 is detectable dorsally at E15 (Fig.…”