The mouse matrix metalloproteinase, epilysin (MMP-28), is alternatively spliced and processed by a furin-like proprotein convertase.
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.
Illman
Sara A
SA
Department of Pathology, Haartman Institute and Biomedicum Helsinki, University of Helsinki and Helsinki University Hospital, Helsinki, FIN-00014, Finland.
Keski-Oja
Jorma
J
Parks
William C
WC
Lohi
Jouko
J
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D006224:Cricetinae; D045683:Furin; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism*; D053505:Matrix Metalloproteinases, Secreted; D051379:Mice; D008969:Molecular Sequence Data; D043484:Proprotein Convertases; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D013381:Subtilisins / Q000378:metabolism*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D043484:Proprotein Convertases; D013381:Subtilisins; D045683:Furin; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; C477998:Mmp28 protein, mouse