发明名称 |
Mammalian Subtilisin/kexin isozyme SKI-1: a proprotein convertase with a unique cleavage specificity |
摘要 |
Using RT-PCR and degenerate oligonucleotides derived from the active site residues of subtilisin-kexin-like serine proteinases, we have identified a highly conserved and phylogenetically ancestral human, rat and mouse type-I membrane-bound proteinase called subtilisin-kexin-isozyme-1 (SKI-1). Computer data bank searches reveals that human SKI-1 was previously cloned but with no identified function. A SKI-1 processed fragment is secreted in culture media in a soluble form. In vitro studies suggest that SKI-1 is a Ca<SUP>2+</SUP>-dependent serine proteinase exhibiting a wide pH optimum for cleavage of proBDNF. Peptides mimicking SKI-1 cleavages sites are also disclosed. SKI-1 prosegment has an ex vivo inhibitory effect on SKI-1 activity. The prosegment is also processed and secreted in culture media. One of its fragments is found tightly associated with the SKI-1 soluble form. Therapeutic applications for SKI-1 inhibitors are disclosed.
|
申请公布号 |
US7211424(B1) |
申请公布日期 |
2007.05.01 |
申请号 |
US19990830837 |
申请日期 |
1999.11.04 |
申请人 |
INSTITUT DE RECHERCHES CLINIQUES DE MONTREAL |
发明人 |
SEIDAH NABIL G.;CHRETIEN MICHEL;MARCINKIEWICZ MIECZYSLAW;REIJO LAAKSONEN;JEAN DAVIGNON |
分类号 |
C12N9/64;G01N33/50;A61K38/00;A61K45/00;A61P1/16;A61P3/06;A61P9/10;A61P25/28;A61P35/00;A61P43/00;C07K1/00;C07K7/06;C07K7/08;C07K16/00;C12N1/15;C12N1/19;C12N1/21;C12N5/10;C12N9/50;C12N15/09;C12N15/57;C12N15/79;C12P21/02;C12Q1/02;C12Q1/37;C12Q1/68;C12R1/91;G01N33/15;G01N33/566;G01N33/573 |
主分类号 |
C12N9/64 |
代理机构 |
|
代理人 |
|
主权项 |
|
地址 |
|