What structure and function of avian plasminogen activator and matrix metalloproteinase-2 reveal about their counterpart mammalian enzymes, their regulation and their role in tumor invasion

被引:10
作者
Alexander, DS
Aimes, RT
Quigley, JP
机构
[1] SUNY STONY BROOK, DEPT CELLULAR & MOL PATHOL, STONY BROOK, NY 11794 USA
[2] SUNY STONY BROOK, DEPT CELLULAR & DEV BIOL, STONY BROOK, NY 11794 USA
关键词
plasminogen activator; metalloprotease; proteases; protease inhibitors; avian uPA; human uPA; regulation;
D O I
10.1159/000468615
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Rous sarcoma virus-transformed chick embryo fibroblasts (RSVCEF) constitute a well-characterized model system for oncogenic transformation, matrix degradation, and cancer invasion. As RSVCEF cultures employ both serine protease and metalloprotease cascades in the process of matrix degradation, they have contributed significantly to understanding the nature and regulation of these molecules involved in invasive cell behavior. RSVCEF produce elevated levels of a matrix metalloprotease-2 (MMP-2) whose hemopexin domain differs from mammalian MMP-2. The majority of MMP-2 produced by RSVCEF is present in a TIMP-free form which enhances its activation, catalytic activity and substrate specificity and therefore its matrix-degrading ability. RSVCEFs also exhibit high levels of urokinase-type plasminogen activator (uPA), which is found in active form in their conditioned medium in complete absence of plasminogen. Recombinantly expressed avian uPA is also in active form, while an active-site mutant of the same maintains its zymogen form, indicating the mechanism of activation of chicken uPA is autocatalytic. A domain and sequence comparison between chicken and human uPA attempts to identify motifs potentially responsible for the zymogen instability of avian uPA and its capability to autoactivate.
引用
收藏
页码:38 / 58
页数:21
相关论文
共 98 条
[61]  
MURPHY G, 1992, J BIOL CHEM, V267, P9612
[62]   METALLOPROTEINASES FROM RABBIT BONE CULTURE-MEDIUM DEGRADE TYPE-IV AND TYPE-V COLLAGENS, LAMININ AND FIBRONECTIN [J].
MURPHY, G ;
CAWSTON, TE ;
GALLOWAY, WA ;
BARNES, MJ ;
BUNNING, RAD ;
MERCER, E ;
REYNOLDS, JJ ;
BURGESON, RE .
BIOCHEMICAL JOURNAL, 1981, 199 (03) :807-811
[63]  
NELLES L, 1987, J BIOL CHEM, V262, P5682
[64]   DIFFERENT DOMAIN INTERACTIONS ARE INVOLVED IN THE BINDING OF TISSUE INHIBITORS OF METALLOPROTEINASES TO STROMELYSIN-1 AND GELATINASE-A [J].
NGUYEN, Q ;
WILLENBROCK, F ;
COCKETT, MI ;
OSHEA, M ;
DOCHERTY, AJP ;
MURPHY, G .
BIOCHEMISTRY, 1994, 33 (08) :2089-2095
[65]  
OKADA Y, 1986, J BIOL CHEM, V261, P14245
[66]  
OSSOWSKI L, 1974, J BIOL CHEM, V249, P4312
[67]  
OVERALL CM, 1990, J BIOL CHEM, V265, P21141
[68]  
PANNELL R, 1987, BLOOD, V69, P22
[69]   QUENCHING OF THE AMIDOLYTIC ACTIVITY OF ONE-CHAIN TISSUE-TYPE PLASMINOGEN-ACTIVATOR BY MUTATION OF LYSINE-416 [J].
PETERSEN, LC ;
BOEL, E ;
JOHANNESSEN, M ;
FOSTER, D .
BIOCHEMISTRY, 1990, 29 (14) :3451-3457
[70]  
PETERSEN LC, 1988, J BIOL CHEM, V263, P11189