UNLABELLED The p90 ribosomal S6 kinase (RSK) family of serine/threonine kinases is expressed in a variety of cancers and its substrate phosphorylation has been implicated in direct regulation of cell survival, proliferation, and cell polarity. This study characterizes and presents the most selective and potent RSK inhibitors known to date, LJH685 and LJI308. Structural analysis confirms binding...

A failure of hemostasis of the organism could cause the formation of clots inside the circulatory system, causing disorders of the system that lead to such processes like the stroke or myocardial infarction. The treatment of these pathologies could require the application of thrombolytic agents like the urokinase (Uk), the tissue type plasminogen activator (tPA) or the streptokinase (Sk). This ...

The protein kinase p90(Rsk) has previously been implicated as a key target of the MAPK pathway during M phase of meiosis II in Xenopus oocytes. To determine whether Rsk is a mediator of MAPK for stimulation of the G(2)/M transition early in meiosis I, we sought to generate a form of Rsk that would be constitutively active in resting, G(2) phase oocytes. Initial studies revealed that an N-termin...

Recombinant desulfatohirudin (HI), a potent and specific thrombin inhibitor, was compared with heparin (HE) as an adjunct to streptokinase thrombolysis. In pentobarbital-anesthetized dogs, an occlusive thrombus (whole blood+thrombin) was introduced into the left anterior descending coronary artery (LAD) with superimposed endothelial damage and distal high-grade stenosis. Intravenous infusion of...

ObJectives. This study sought to examine the incidence, temporal profile and clinical implications of shock in a large trial of thrombolytic therapy for acute myocardial infarction. Background. Despite advances in the treatment of acute ischemic syndromes, cardiogenic shock remains associated with significant morbidity and mortality. Methods. Patients who presented within 6 h of symptom onset w...

The p90 ribosomal S6 kinase (RSK) is a family of MAPK-activated serine/threonine kinases (RSK1-4) whose expression and/or activity are deregulated in several cancers, including breast cancer. Up-regulation of RSKs promotes cellular processes that drive tumorigenesis in Triple Negative Breast Cancer (TNBC) cells. Although RSKs regulate protein synthesis in certain cell types, the role of RSK-med...

T he widespread application of plasminogen activators in the treatment of myocardial infarction has resulted in a significant reduction in mortality.",2 Most patients have been treated with two very different drugs: streptokinase, a bacterial protein that is the product of fermentation technology dating from the 1930s, and recombinant tissue-type plasminogen activator (rt-PA), a human protein t...

Rsk kinases play important roles in several cellular processes such as proliferation, metabolism, and migration. Until recently, Rsk activation was thought to be exclusively initiated by Erk1/2, but in dendritic cells (DC) Rsk is also activated by p38 mitogen-activated protein (MAP) kinase via its downstream substrates, MK2/3. How and why this noncanonical configuration of the MAP kinase pathwa...

Fibrinolytic therapy has an expanding role in the treatment of many thromboembolic disorders. Four fibrinolytic drugs are currently marketed: streptokinase, anisoylated plasminogen-streptokinase activator complex, urokinase, and recombinant human tissue-type plasminogen activator. All 4 of these drugs activate the fibrinolytic system by converting plasminogen to the active enzyme, plasmin. Plas...

Metastasis, the spreading of cancer cells from a primary tumor to secondary sites throughout the body, is the primary cause of death for patients with cancer. New therapies that prevent invasion and metastasis in combination with current treatments could therefore significantly reduce cancer recurrence and morbidity. Metastasis is driven by altered signaling pathways that induce changes in cell...