G. Kassam et al., The p11 subunit of the annexin II tetramer plays a key role in the stimulation of t-PA-dependent plasminogen activation, BIOCHEM, 37(48), 1998, pp. 16958-16966
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 stimul
ate t-PA-dependent [Glu]plasminogen activation. The fluid-phase recombinant
p11 subunit stimulated the rate of t-PA-dependent activation of [Glu]plasm
inogen about 46-fold compared to an approximate stimulation of 2-fold by th
e 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 ac
id. Both Ant and the p11 subunit protected t-PA and plasmin from inactivati
on by PAI-1 and alpha(2)-antiplasmin, respectively. A peptide to the C term
inus of the p11 subunit (85-Y-F-V-V-H-M-K-Q-K-G-K-K-96) inhibited the p11-d
ependent stimulation of t-PA-dependent plasminogen activation. In addition,
a deletion mutant of the p11 subunit, missing the last mio C-terminal lysi
ne residues, retained only about 15% of the activity of the wild-type p11 s
ubunit. Similarly, a mutant Ant composed of the wild-type p36 subunit and t
he p11 subunit deletion mutant possessed about 12% of the wild-type activit
y. These results, therefore, suggest that the C-terminal lysine residues of
the p11 subunit bind plasminogen and participate in the stimulation of t-P
A-dependent activation of plasminogen by AIIt.