Mitogen-activated protein kinase (MAPK) signaling regulates fundamental cellular functions including proliferation, differentiation, and survival. We have demonstrated previously that inhibiting MAPK signaling induces apoptosis in melanoma cells but not in normal melanocytes, suggesting that the MAPK pathway propagates essential survival signals in melanoma cells. Here, we report that the 90-kD...

The triple-negative breast cancer (TNBC) subtype is enriched in cancer stem cells (CSCs) and clinically correlated with the highest rate of recurrence. Several studies implicate the RSK pathway as being pivotal for the growth and proliferation of CSCs, which are postulated to drive tumor relapse. We now address the potential for the newly developed RSK inhibitor LJI308 to target the CSC populat...

BACKGROUND A major limitation of streptokinase is the development and persistence of problematic neutralizing antibodies that have the potential to limit the effectiveness of repeat streptokinase therapy. Accordingly, tissue-type plasminogen activator (t-PA) is frequently administered to patients with recurrent infarction presenting more than four days from previous treatment with streptokinase...

the measurement of anti-streptokinase antibodies can distinguish the patients who may benefit from streptokinase and those who should be treated with some other thrombolytic regimen. neutralising titration test is a commonly used classical assay for measuring anti-streptokinase antibodies and in this assay the ability of anti-streptokinase antibodies in patients' sera in preventing the lytic ef...

Streptokinase is shown to react with either human plasmin or human plasminogen to form an equimolar product which migrates in starch gel electrophoresis at pH 6.0 or 8.0 with a migration rate intermediate between the rates of migration of the two proteins. When streptokinase was present in molar excess in the reaction mixtures, the uncombined streptokinase displayed a migration rate at pH 6.0 (...

The risk of bleeding associated with intracoronary infusion of streptokinase in acute myocardial infarction was determined in a randomised controlled trial containing 302 patients under the age of 70. Intracoronary streptokinase infusion was given to 152 patients and 150 patients were treated conventionally. Bleeding was seen in 24 (16%) patients in the streptokinase group and in two of the con...

Streptokinase, an extracellular protein produced by Streptococci, is capable of activating the human fibrinolytic zymogen plasminogen. The rate of amidolytic activity of the plasminogen-streptokinase complex is greatly diminished by micromolar concentrations of ATP and heparin oligosaccharides. In addition, the plasminogen activator activity of the plasminogen-streptokinase complex is also inhi...

Activation of the various mitogen-activated protein (MAP) kinase pathways converts many different extracellular stimuli into specific cellular responses by inducing the phosphorylation of particular groups of substrates. One important determinant for substrate specificity is likely to be the amino-acid sequence surrounding the phosphorylation site; however, these sites overlap significantly bet...

Ataxia telangiectasia mutant (ATM) is an S/T-Q-directed kinase that is critical for the cellular response to double-stranded breaks (DSBs) in DNA. Following DNA damage, ATM is activated and recruited by the MRN protein complex [meiotic recombination 11 (Mre11)/DNA repair protein Rad50/Nijmegen breakage syndrome 1 proteins] to sites of DNA damage where ATM phosphorylates multiple substrates to t...

AXL receptor tyrosine kinase (RTK) inhibition presents a promising therapeutic strategy for aggressive tumor subtypes, as AXL signaling is upregulated in many cancers resistant to first-line treatments. Furthermore, the AXL ligand growth arrest-specific gene 6 (GAS6) has recently been linked to cancer drug resistance. Here, we established that challenging conditions, such as serum deprivation, ...