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A novel class of tyrosine kinase blockers represented by the tyrphostins AG1295 and AG1296 is described. These compounds inhibit selectively the platelet-derived growth factor (PDGF) receptor kinase and the PDGF-dependent DNA synthesis in Swiss 3T3 cells and in porcine aorta endothelial cells with 50% inhibitory concentrations below 5 and 1 microM,(More)
Signaling through receptor tyrosine kinases (RTKs) is a major mechanism for intercellular communication during development and in the adult organism, as well as in disease-associated processes. The phosphorylation status and signaling activity of RTKs is determined not only by the kinase activity of the RTK but also by the activities of protein tyrosine(More)
G protein-coupled receptors (GPCRs) represent a major class of drug targets. Recent investigation of GPCR signaling has revealed interesting novel features of their signal transduction pathways which may be of great relevance to drug application and the development of novel drugs. Firstly, a single class of GPCRs such as the bradykinin type 2 receptor (B2R)(More)
Tyrosine phosphorylation is an important signalling mechanism in eukaryotic cells. In cancer, oncogenic activation of tyrosine kinases is a common feature, and novel anticancer drugs have been introduced that target these enzymes. Tyrosine phosphorylation is also controlled by protein-tyrosine phosphatases (PTPs). Recent evidence has shown that PTPs can(More)
Many agonists of G-protein-coupled receptors (GPCRs) can stimulate receptor tyrosine kinases and the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway. A 'transactivation' mechanism, which links these events in one signalling chain, inspired many researchers, but inevitably raised new questions. A 'multi-track'(More)
Inappropriate activation of oncogenic kinases at intracellular locations is frequently observed in human cancers, but its effects on global signaling are incompletely understood. Here, we show that the oncogenic mutant of Flt3 (Flt3-ITD), when localized at the endoplasmic reticulum (ER), aberrantly activates STAT5 and upregulates its targets, Pim-1/2, but(More)
p120-catenin (p120(ctn)) interacts with the cytoplasmic tail of cadherins and is thought to regulate cadherin clustering during formation of adherens junctions. Several observations suggest that p120 can both positively and negatively regulate cadherin adhesiveness depending on signals that so far remain unidentified. Although p120 tyrosine phosphorylation(More)
Oxidation of the catalytic cysteine of protein-tyrosine phosphatases (PTP), which leads to their reversible inactivation, has emerged as an important regulatory mechanism linking cellular tyrosine phosphorylation and signalling by reactive-oxygen or -nitrogen species (ROS, RNS). This review focuses on recent findings about the involved pathways, enzymes and(More)
There is evidence that consumption of certain dietary ingredients may favourably modulate biotransformation of carcinogens. Associated with this is the hypothesis that the risk for developing colorectal cancer could be reduced, since its incidence is related to diet. Two main groups of biotransformation enzymes metabolize carcinogens, namely Phase I(More)
Fms-like tyrosine kinase 3 (FLT3) plays an important role in hematopoietic differentiation, and constitutively active FLT3 mutant proteins contribute to the development of acute myeloid leukemia. Little is known about the protein-tyrosine phosphatases (PTP) affecting the signaling activity of FLT3. To identify such PTP, myeloid cells expressing wild type(More)