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10.1161/01.res.0000024412.24491.ca http://scihub22266oqcxt.onion/10.1161/01.res.0000024412.24491.ca 12114320!ä!12114320 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Circ+Res 2002 ; 91 (1): 38-45 Nephropedia Template TP {{tp|p=12114320|t=2002. Hypoxic induction of the hypoxia-inducible factor is mediated via the adaptor protein Shc in endothelial cells |pdf=|usr=}}{{12114320}} gab.com Text Hypoxic induction of the hypoxia-inducible factor is mediated via the adaptor protein Shc in endothelial cells JO: Circ Res http://www.kidney.de/pget.php?&tw=1&pmid=12114320 #FOAvip Tyrosine kinase cascades may play a role in the hypoxic regulation of hypoxia-inducible factor (HIF)-1. We investigated the role of tyrosine kinase phosphorylation and of the Shc/Ras cascade on hypoxic HIF-1 stabilization. Exposure of human umbilical vein endothelial cells to hypoxia results in HIF protein stabilization as early as 10 minutes, with a maximum at 3 hours, and also in Shc tyrosine phosphorylation, with a maximum at 10 minutes. To test whether Shc directly mediates hypoxia-induced HIF stabilization, human umbilical vein endothelial cells were transfected with a dominant-negative Shc mutant (dnShc), resulting in significantly reduced HIF protein levels compared with control. Similar results were obtained with cells transfected with dominant-negative Ras, a known downstream effector of Shc. Hypoxia-induced Ras activity was significantly reduced in cells transfected with dnShc compared with control levels, indicating that Ras indeed acts downstream from Shc. Moreover, cells pretreated with a specific Raf-1 kinase inhibitor, a known downstream effector of Ras, exhibited reduced HIF protein levels. To examine the functional consequences of Shc in hypoxic signaling, HIF-1 ubiquitination, protein stabilization, and endothelial cell migration were assessed. Overexpression of dnShc increased ubiquitination of HIF-1 and reduced the half-life of the protein. Moreover, dnShc, dominant-negative Ras, or the Raf-1 kinase inhibitor significantly inhibited migration under hypoxia. Thus, Shc in concert with Ras and Raf-1 contributes to hypoxia-induced HIF-1alpha protein stabilization and endothelial cell migration. Twit Text FOAVip Hypoxic induction of the hypoxia-inducible factor is mediated via the adaptor protein Shc in endothelial cells ????Circ Res http://www.kidney.de/pget.php?&tw=1&pmid=12114320 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=12114320 #FOAvip English Wikipedia <ref>{{Cite pmid|12114320}}</ref> Hypoxic induction of the hypoxia-inducible factor is mediated via the adaptor protein Shc in endothelial cells #MMPMID12114320 Jung F; Haendeler J; Hoffmann J; Reissner A; Dernbach E; Zeiher AM; Dimmeler S Circ Res 2002[Jul]; 91 (1): 38-45 PMID12114320show ga Tyrosine kinase cascades may play a role in the hypoxic regulation of hypoxia-inducible factor (HIF)-1. We investigated the role of tyrosine kinase phosphorylation and of the Shc/Ras cascade on hypoxic HIF-1 stabilization. Exposure of human umbilical vein endothelial cells to hypoxia results in HIF protein stabilization as early as 10 minutes, with a maximum at 3 hours, and also in Shc tyrosine phosphorylation, with a maximum at 10 minutes. To test whether Shc directly mediates hypoxia-induced HIF stabilization, human umbilical vein endothelial cells were transfected with a dominant-negative Shc mutant (dnShc), resulting in significantly reduced HIF protein levels compared with control. Similar results were obtained with cells transfected with dominant-negative Ras, a known downstream effector of Shc. Hypoxia-induced Ras activity was significantly reduced in cells transfected with dnShc compared with control levels, indicating that Ras indeed acts downstream from Shc. Moreover, cells pretreated with a specific Raf-1 kinase inhibitor, a known downstream effector of Ras, exhibited reduced HIF protein levels. To examine the functional consequences of Shc in hypoxic signaling, HIF-1 ubiquitination, protein stabilization, and endothelial cell migration were assessed. Overexpression of dnShc increased ubiquitination of HIF-1 and reduced the half-life of the protein. Moreover, dnShc, dominant-negative Ras, or the Raf-1 kinase inhibitor significantly inhibited migration under hypoxia. Thus, Shc in concert with Ras and Raf-1 contributes to hypoxia-induced HIF-1alpha protein stabilization and endothelial cell migration. |*Adaptor Proteins, Signal Transducing[MESH] |*Adaptor Proteins, Vesicular Transport[MESH] |*Transcription Factors[MESH] |Blotting, Western[MESH] |Cell Hypoxia/physiology[MESH] |Cell Line[MESH] |Cell Movement/drug effects[MESH] |Cobalt/pharmacology[MESH] |Cycloheximide/pharmacology[MESH] |DNA-Binding Proteins/*metabolism[MESH] |Endothelium, Vascular/cytology/drug effects/*metabolism[MESH] |Enzyme Inhibitors/pharmacology[MESH] |Humans[MESH] |Hypoxia-Inducible Factor 1[MESH] |Hypoxia-Inducible Factor 1, alpha Subunit[MESH] |Mutation[MESH] |Nuclear Proteins/*metabolism[MESH] |Plasmids/genetics[MESH] |Proteins/genetics/*metabolism[MESH] |Proto-Oncogene Proteins c-raf/antagonists & inhibitors/metabolism[MESH] |Pyrazoles/pharmacology[MESH] |Pyrimidines/pharmacology[MESH] |Shc Signaling Adaptor Proteins[MESH] |Src Homology 2 Domain-Containing, Transforming Protein 1[MESH] |Transfection[MESH] |Tyrphostins/pharmacology[MESH] |Ubiquitin/metabolism[MESH] |ras Proteins/genetics/metabolism[MESH]Hypoxic induction of the hypoxia-inducible factor is mediated via the (epmc).pdf DeepDyve Pubget Overpricing