The p11 subunit of the annexin II tetramer plays a key role in the stimulation of t-PA-dependent plasminogen activation

被引:117
作者
Kassam, G [1 ]
Le, BH [1 ]
Choi, KS [1 ]
Kang, HM [1 ]
Fitzpatrick, SL [1 ]
Louie, P [1 ]
Waisman, DM [1 ]
机构
[1] Univ Calgary, Dept Biochem & Mol Biol, Canc Biol Res Grp, Calgary, AB T2N 4N1, Canada
关键词
D O I
10.1021/bi981713l
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
Annexin II tetramer (AIIt) is an important endothelial cell surface protein receptor for plasminogen and t-PA. AIIt, a heterotetramer, is composed of two p36 subunits (called annexin II) and two p11 subunits. In this report, we have compared the ability of the isolated p36 and p11 subunits to stimulate t-PA-dependent [Glu]plasminogen activation. The fluid-phase recombinant p11 subunit stimulated the rate of t-PA-dependent activation of [Glu]plasminogen about 46-fold compared to an approximate stimulation of 2-fold by the recombinant p36 subunit and 77-fold by recombinant AIIt, The stimulation of t-PA-dependent activation of [Glu]plasminogen by the p11 subunit was Ca2+-independent and inhibited by E-aminocaproic acid. [Glu]Plasminogen bound to a p11 subunit affinity column and could be eluted with E-aminocaproic acid. Both Ant and the p11 subunit protected t-PA and plasmin from inactivation by PAI-1 and alpha(2)-antiplasmin, respectively. A peptide to the C terminus of the p11 subunit (85-Y-F-V-V-H-M-K-Q-K-G-K-K-96) inhibited the p11-dependent stimulation of t-PA-dependent plasminogen activation. In addition, a deletion mutant of the p11 subunit, missing the last mio C-terminal lysine residues, retained only about 15% of the activity of the wild-type p11 subunit. Similarly, a mutant Ant composed of the wild-type p36 subunit and the p11 subunit deletion mutant possessed about 12% of the wild-type activity. These results, therefore, suggest that the C-terminal lysine residues of the p11 subunit bind plasminogen and participate in the stimulation of t-PA-dependent activation of plasminogen by AIIt.
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页码:16958 / 16966
页数:9
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