Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropilin-1 (Np-1), a receptor for semaphorin 3A and vascular endothelial growth factor, is expressed at high levels in pancreatic ductal adenocarcinoma (PDAC). To assess the potential role of Np-1 in PDAC, COLO-357 pancreatic cancer cells, which express relatively low levels of Np-1, were stably transfected with the Np-1 cDNA. Np-1 overexpression was associated with enhanced cell invasiveness in response to hepatocyte growth factor (HGF), and this effect was abolished by small interfering RNA-mediated down-regulation of c-Met. Conversely, in PANC-1 pancreatic cancer cells, which express relatively high levels of Np-1, suppression of endogenous Np-1 completely abolished HGF-mediated cell invasion. To determine which pathways are involved in Np-1-mediated facilitation of c-Met-dependent cell invasiveness, the effects of HGF on signaling were examined next in sham-transfected and Np-1-overexpressing COLO-357 cells. HGF actions on c-Met tyrosine phosphorylation and p38 mitogen-activated protein kinase (MAPK) activation were increased in Np-1-overexpressing COLO-357 cells by comparison with HGF effects in sham-transfected cells. SB203580, an inhibitor of p38 MAPK, suppressed HGF-induced invasion in Np-1-overexpressing cells, whereas U0126, a MAP/extracellular signal-regulated kinase kinase inhibitor, was without effect. PP2, a Src inhibitor, and LY294002, a phosphatidylinositol 3-kinase inhibitor, also suppressed HGF-induced invasion in these cells. Immunoprecipitation studies revealed that Np-1 associated with c-Met, but not with epidermal growth factor receptor, family members. Confocal microscopy indicated that this association occurred on the plasma membrane and that HGF promoted the internalization of Np-1-c-Met complex, leading to its perinuclear localization. These findings indicate that Np-1 is required for efficient activation of c-Met-dependent pathways that promote cell invasiveness.
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PMID:Hepatocyte growth factor-mediated cell invasion in pancreatic cancer cells is dependent on neuropilin-1. 1797 73

Neurons concentrate mitochondria at sites in the cell that have a high demand for ATP and/or calcium buffering. To accomplish this, mitochondrial transport and docking are thought to respond to intracellular signaling pathways. However, the cell might also concentrate mitochondrial function by locally modulating mitochondrial activity. We tested this hypothesis by measuring the membrane potential of individual mitochondria throughout the axons of chick sensory neurons using the dye tetramethylrhodamine methylester (TMRM). We found no difference in the TMRM mitochondrial-to-cytoplasmic fluorescence ratio (F(m)/F(c)) among three functionally distinct regions: axonal branch points, distal axons, and the remaining axon shaft. In addition, we found no difference in F(m)/F(c) among stationary, retrogradely moving, or anterogradely moving mitochondria. However, F(m)/F(c) was significantly higher in the lamellipodia of growth cones, and among a small fraction of mitochondria throughout the axon. To identify possible signals controlling membrane potential, we used beads covalently coupled to survival and guidance cues to provide a local stimulus along the axon shaft. NGF- or semaphorin 3A-coupled beads caused a significant increase in F(m)/F(c) in the immediately adjacent region of axon, and this was diminished in the presence of the PI3 (phosphatidylinositol-3) kinase inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] or the MAP (mitogen-activated protein) kinase inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-amino-phenylthio]butadiene), demonstrating that signaling pathways downstream of both ligands affect the DeltaPsi(m) of mitochondria. In addition, general inhibition of receptor tyrosine kinase activity produced a profound global decrease in F(m)/F(c). Thus, two guidance molecules that exert different effects on growth cone motility both elicit local, receptor-mediated increases in membrane potential.
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PMID:Mitochondrial membrane potential in axons increases with local nerve growth factor or semaphorin signaling. 1870 93