siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5) P-3-mTOR signaling pathway as a primary regulator of transferrin uptake

Cited 48 time in webofscience Cited 0 time in scopus
  • Hit : 458
  • Download : 0
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 non-transformed 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 vesicle without affecting endocytosis or recycling rates. Conclusion: Our study identifies the PtdIns( 3,4,5) P3-mTOR signaling pathway as a new regulator of iron-transferrin uptake and serves as a proof-of-concept that targeted RNA interference screens of the signaling proteome provide a powerful and unbiased approach to discover or rank signaling pathways that regulate a particular cell function.
Publisher
BIOMED CENTRAL LTD
Issue Date
2007
Language
English
Article Type
Article
Keywords

MAMMALIAN TARGET; MEDIATED ENDOCYTOSIS; RECEPTOR GENE; CELL; MTOR; IRON; EXPRESSION; RAPAMYCIN; ACTIVATION; GROWTH

Citation

GENOME BIOLOGY, v.8, no.7

ISSN
1474-7596
DOI
10.1186/gb-2007-8-7-r142
URI
http://hdl.handle.net/10203/90427
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 48 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0