TAILIEUCHUNG - Báo cáo khóa học: Nerve growth factor mediates activation of the Smad pathway in PC12 cells

Ligand-induced oligomerization of receptors is a key step in initiating growth factor signaling. Nevertheless, complex biological responses often require additionaltrans-signaling mechanisms involving two or more signaling cascades. For cells of neuronal origin, it was shown that neurotrophic effects evoked by nerve growth factor or other neurotro-phins dependhighlyon the cooperativitywith cytokines that belong to the transforming growth factor b (TGF-b) superfamily. We found that rat pheochromocytoma cells, which represent amodel systemfor neuronal differentiation, are unresponsive to TGF-b1 due to limiting levels of its receptor, TbRII | Eur. J. Biochem. 271 920-931 2004 FEBS 2004 doi Nerve growth factor mediates activation of the Smad pathway in PC12 cells Marion Lutz1 Kerstin Krieglstein2 Simone Schmitt1 Peter ten Dijke3 Walter Sebald1 Andrea Wizenmann4 and Petra Knaus1 1 Department of Physiological Chemistry II Biocenter University of Wurzburg Germany department of Anatomy University of Gottingen Germany 3Division of Cellular Biochemistry the Netherlands Cancer Institute Amsterdam the Netherlands 4JRG of Developmental Neurobiology Biocenter University of Wurzburg Germany Ligand-induced oligomerization of receptors is a key step in initiating growth factor signaling. Nevertheless complex biological responses often require additional trans-signaling mechanisms involving two or more signaling cascades. For cells of neuronal origin it was shown that neurotrophic effects evoked by nerve growth factor or other neurotro-phins depend highly on the cooperativity with cytokines that belong to the transforming growth factor b TGF-b superfamily. We found that rat pheochromocytoma cells which represent a model system for neuronal differentiation are unresponsive to TGF-b1 due to limiting levels of its receptor TbRII. However stimulation with nerve growth factor leads to activation of the Smad pathway independent of TGF-b. In contrast to TGF-b signaling activation of Smad3 by nerve growth factor does not occur via phosphorylation of the C-terminal SSXS-motif but leads to hetero meric complexformation with Smad4 nuclear translocation of Smad3 and transcriptional activation of Smad-dependent reporter genes. This response is direct and does not require de novo protein synthesis as shown by cycloheximide treatment. This initiation of transcription is dependent on functional tyrosine kinase receptors and can be blocked by Smad7. These data provide further evidence that the Smad proteins are not exclusively activated by the classical TGF-b triggered mechanism. The potential of NGF .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• Structural biochemistry
• bacteria
• chemical reaction
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• Crystal structure
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine