tailieunhanh - Báo cáo y học: " siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P3-mTOR signaling pathway as a primary regulator of transferrin uptak"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P3-mTOR signaling pathway as a primary regulator of transferrin uptake. | Open Access siRNA screen of the human signaling proteome identifies the PtdIns 3 4 5 P3-mTOR signaling pathway as a primary regulator of transferrin uptake Thierry Galvez Mary N Teruel Won Do Heo Joshua T Jones Man Lyang Kim Jen Liou Jason W Myers and Tobias Meyer Address Department of Chemical and Systems Biology and Bio-X Program Stanford University School of Medicine Stanford CA 94305 USA. Correspondence Thierry Galvez. Email galvez@. Tobias Meyer. Email tobias1@ Published 19 July 2007 Genome Biology 2007 8 R142 doi gb-2007-8-7-r142 The electronic version of this article is the complete one and can be found online at http 2007 8 7 R142 Received 16 February 2007 Revised 30 May 2007 Accepted 19 July 2007 2007 Galvez et al. licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Background Iron uptake via endocytosis of iron-transferrin-transferrin receptor complexes is a rate-limiting step for cell growth viability and proliferation in tumor cells as well as nontransformed cells such as activated lymphocytes. Signaling pathways that regulate transferrin uptake have not yet been identified. Results We surveyed the human signaling proteome for regulators that increase or decrease transferrin uptake by screening 1 804 dicer-generated signaling small interfering RNAs using automated quantitative imaging. In addition to known transport proteins we identified 11 signaling proteins that included a striking signature set for the phosphatidylinositol-3 4 5-trisphosphate PtdIns 3 4 5 P3 -target of rapamycin mTOR signaling pathway. We show that the PI3K-mTOR signaling pathway is a positive regulator of transferrin uptake that increases the number of transferrin receptors per endocytic