Plasminogen (Pg) activators such as streptokinase (SK) save lives by generating plasmin to dissolve blood clots. Some believe that the unique ability of SK to activate Pg in the absence of fibrin limits its therapeutic utility. We have found that SK contains an unusual NH(2)-terminal "catalytic switch" that allows Pg activation through both fibrin-independent and fibrin-dependent mechanisms. Un...

Objective—Angiotensin II (Ang II) promotes vascular inflammation and remodeling via activation of nuclear factor B (NFB)–mediated transcription of proinflammatory genes such as interleukin-6 (IL-6). We examined the signaling mechanism whereby Ang II activates NFB in vascular smooth muscle cells (VSMCs). Methods and Results—Ang II treatment did not increase phosphorylation of inhibitor of B (I B...

The therapeutic properties of plasminogen activators are dictated by their mechanism of action. Unlike staphylokinase, a single domain protein, streptokinase, a 3-domain (alpha, beta, and gamma) molecule, nonproteolytically activates human (h)-plasminogen and protects plasmin from inactivation by alpha(2)-antiplasmin. Because a streptokinase-like mechanism was hypothesized to require the strept...

DETERMINATION OF STREPTOKINASE ACTIVITY IS USUALLY ACCOMPLISHED THROUGH TWO ASSAY METHODS: a) Clot lysis, b) Chromogenic substrate assay. In this study the biological activity of two streptokinase products, namely Streptase®, which is a native product and Heberkinasa®, which is a recombinant product, was determined against the third international reference standard using the two forementioned a...

Introduction: Thrombosis and the blockage of blood vessels with clots, can lead to acute myocardial infarction and some times even death. Aside from surgical interventions to remove the blockage, the only available treatment is the administration of thrombolytic agents to dissolve the blood clot. Streptokinase (SK) is the most commonly used fibrinolytic drug for this purpose. However, SK...

p90 ribosomal S6 kinase (RSK) is an important downstream effector of mitogen-activated protein kinase, but its biological functions are not well understood. We have now identified the first small-molecule, RSK-specific inhibitor, which we isolated from the tropical plant Forsteronia refracta. We have named this novel inhibitor SL0101. SL0101 shows remarkable specificity for RSK. The major deter...

RSK is normally defined in terms of a somewhat complicated procedure called row-insertion. This definition unfortunately masks the remarkable symmetry property that if A RSK 7−−−→ (P,Q) then At RSK 7−−−→ (Q,P ). Here we present an alternate description of RSK via local transformations that makes the symmetry obvious. Our approach is thus similar in spirit to the growth diagrams of Fomin [6]. In...