The p11 Subunit of the Annexin II Tetramer Plays a Key Role in the Stimulation of t-PA-Dependent Plasminogen Activation
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- 作者：Geetha Kassam ; Bich-Hang Le ; Kyu-Sil Choi ; Hyoung-Min Kang ; Sandra L. Fitzpatrick ; Peter Louie ; and David M. Waisman
- 刊名：Biochemistry
- 出版年：1998
- 出版时间：December 1, 1998
- 年：1998
- 卷：37
- 期：48
- 页码：16958 - 16966
- 全文大小：139K
- 年卷期：v.37,no.48(December 1, 1998)
- ISSN：1520-4995
文摘
Annexin II tetramer (AIIt) is an important endothelial cell surface protein receptor forplasminogen and t-PA. AIIt, a heterotetramer, is composed of two p36 subunits (called annexin II) andtwo p11 subunits. In this report, we have compared the ability of the isolated p36 and p11 subunits tostimulate t-PA-dependent [Glu]plasminogen activation. The fluid-phase recombinant p11 subunit stimulatedthe rate of t-PA-dependent activation of [Glu]plasminogen about 46-fold compared to an approximatestimulation of 2-fold by the recombinant p36 subunit and 77-fold by recombinant AIIt. The stimulationof t-PA-dependent activation of [Glu]plasminogen by the p11 subunit was Ca2+-independent and inhibitedby 
-aminocaproic acid. [Glu]Plasminogen bound to a p11 subunit affinity column and could be elutedwith -aminocaproic acid. Both AIIt and the p11 subunit protected t-PA and plasmin from inactivationby PAI-1 and 
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 plasminogenactivation. In addition, a deletion mutant of the p11 subunit, missing the last two C-terminal lysine residues,retained only about 15% of the activity of the wild-type p11 subunit. Similarly, a mutant AIIt composedof the wild-type p36 subunit and the p11 subunit deletion mutant possessed about 12% of the wild-typeactivity. These results, therefore, suggest that the C-terminal lysine residues of the p11 subunit bindplasminogen and participate in the stimulation of t-PA-dependent activation of plasminogen by AIIt.
-aminocaproic acid. [Glu]Plasminogen bound to a p11 subunit affinity column and could be elutedwith -aminocaproic acid. Both AIIt and the p11 subunit protected t-PA and plasmin from inactivationby PAI-1 and 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 plasminogenactivation. In addition, a deletion mutant of the p11 subunit, missing the last two C-terminal lysine residues,retained only about 15% of the activity of the wild-type p11 subunit. Similarly, a mutant AIIt composedof the wild-type p36 subunit and the p11 subunit deletion mutant possessed about 12% of the wild-typeactivity. These results, therefore, suggest that the C-terminal lysine residues of the p11 subunit bindplasminogen and participate in the stimulation of t-PA-dependent activation of plasminogen by AIIt.