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10.18632/oncotarget.7639 http://scihub22266oqcxt.onion/10.18632/oncotarget.7639 C4905435!4905435 !26919114     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26919114 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Oncotarget 2016 ; 7 (10 ): 10739-55 Nephropedia Template TP {{tp|p=26919114 |t=2016. MPL W515L expression induces TGF? secretion and leads to an increase in chemokinesis via phosphorylation of THOC5 |pdf=|usr=}}{{26919114 }} gab.com Text MPL W515L expression induces TGF secretion and leads to an increase in chemokinesis via phosphorylation of THOC5 JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=26919114 #FOAvip The thrombopoietin receptor (MPL) has been shown to be mutated (MPL W515L) in myelofibrosis and thrombocytosis yet new approaches to treat this disorder are still required. We have previously shown that transcriptome and proteomic effects do not correlate well in oncogene-mediated leukemogenesis. We therefore investigated the effects of MPL W515L using proteomics. The consequences of MPL W515L expression on over 3300 nuclear and 3500 cytoplasmic proteins were assessed using relative quantification mass spectrometry. We demonstrate that MPL W515L expression markedly modulates the CXCL12/CXCR4/CD45 pathway associated with stem and progenitor cell chemotactic movement. We also demonstrated that MPL W515L expressing cells displayed increased chemokinesis which required the MPL W515L-mediated dysregulation of MYC expression via phosphorylation of the RNA transport protein THOC5 on tyrosine 225. In addition MPL W515L expression induced TGF? secretion which is linked to sphingosine 1-phosphate production and the increased chemokinesis. These studies identify several pathways which offer potential targets for therapeutic intervention in the treatment of MPL W515L-driven malignancy. We validate our approach by showing that CD34+ cells from MPL W515L positive patients display increased chemokinesis and that treatment with a combination of MYC and sphingosine kinase inhibitors leads to the preferential killing of MPL W515L expressing cells. Twit Text FOAVip MPL W515L expression induces TGF secretion and leads to an increase in chemokinesis via phosphorylation of THOC5 ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=26919114 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26919114 #FOAvip English Wikipedia <ref>{{Cite pmid|26919114 }}</ref> MPL W515L expression induces TGF? secretion and leads to an increase in chemokinesis via phosphorylation of THOC5 #MMPMID26919114 Whetton AD ; Azmi NC ; Pearson S ; Jaworska E ; Zhang L ; Blance R ; Kendall AC ; Nicolaou A ; Taylor S ; Williamson AJ ; Pierce A Oncotarget 2016[Mar]; 7 (10 ): 10739-55 PMID26919114 show ga The thrombopoietin receptor (MPL) has been shown to be mutated (MPL W515L) in myelofibrosis and thrombocytosis yet new approaches to treat this disorder are still required. We have previously shown that transcriptome and proteomic effects do not correlate well in oncogene-mediated leukemogenesis. We therefore investigated the effects of MPL W515L using proteomics. The consequences of MPL W515L expression on over 3300 nuclear and 3500 cytoplasmic proteins were assessed using relative quantification mass spectrometry. We demonstrate that MPL W515L expression markedly modulates the CXCL12/CXCR4/CD45 pathway associated with stem and progenitor cell chemotactic movement. We also demonstrated that MPL W515L expressing cells displayed increased chemokinesis which required the MPL W515L-mediated dysregulation of MYC expression via phosphorylation of the RNA transport protein THOC5 on tyrosine 225. In addition MPL W515L expression induced TGF? secretion which is linked to sphingosine 1-phosphate production and the increased chemokinesis. These studies identify several pathways which offer potential targets for therapeutic intervention in the treatment of MPL W515L-driven malignancy. We validate our approach by showing that CD34+ cells from MPL W515L positive patients display increased chemokinesis and that treatment with a combination of MYC and sphingosine kinase inhibitors leads to the preferential killing of MPL W515L expressing cells. |Animals [MESH] |Case-Control Studies [MESH] |Cell Line, Tumor [MESH] |Cell Movement/physiology [MESH] |Cell Proliferation/physiology [MESH] |Cells, Cultured [MESH] |Humans [MESH] |Mice [MESH] |Myeloproliferative Disorders/genetics/metabolism/pathology [MESH] |Nuclear Proteins/genetics/*metabolism [MESH] |Phosphorylation [MESH] |Receptors, Thrombopoietin/*biosynthesis/genetics/metabolism [MESH] |Signal Transduction [MESH]MPL W515L expression induces TGF? secretion and leads to an increase i(epmc).pdf DeepDyve Pubget Overpricing