Survey of Activated FLT3 Signaling in Leukemia

DSpace/Manakin Repository

Survey of Activated FLT3 Signaling in Leukemia

Citable link to this page

. . . . . .

Title: Survey of Activated FLT3 Signaling in Leukemia
Author: Gu, Ting-lei; Nardone, Julie; Loriaux, Marc; Tucker, Meghan; Kornhauser, Jon; Ren, Jianmin; MacNeill, Joan; Druker, Brian J.; Heinrich, Michael C.; Rush, John; Polakiewicz, Roberto D.; Villén, Judit; Gygi, Steven P.; Beausoleil, Sean A; Wang, Yi

Note: Order does not necessarily reflect citation order of authors.

Citation: Gu, Ting-lei, Julie Nardone, Yi Wang, Marc Loriaux, Judit Villén, Sean Beausoleil, Meghan Tucker, et al. 2011. Survey of activated FLT3 signaling in leukemia. PLoS ONE 6(4): e19169.
Full Text & Related Files:
Abstract: Activating mutations of FMS-like tyrosine kinase-3 (FLT3) are found in approximately 30% of patients with acute myeloid leukemia (AML). FLT3 is therefore an attractive drug target. However, the molecular mechanisms by which FLT3 mutations lead to cell transformation in AML remain unclear. To develop a better understanding of FLT3 signaling as well as its downstream effectors, we performed detailed phosphoproteomic analysis of FLT3 signaling in human leukemia cells. We identified over 1000 tyrosine phosphorylation sites from about 750 proteins in both AML (wild type and mutant FLT3) and B cell acute lymphoblastic leukemia (normal and amplification of FLT3) cell lines. Furthermore, using stable isotope labeling by amino acids in cell culture (SILAC), we were able to quantified over 400 phosphorylation sites (pTyr, pSer, and pThr) that were responsive to FLT3 inhibition in FLT3 driven human leukemia cell lines. We also extended this phosphoproteomic analysis on bone marrow from primary AML patient samples, and identify over 200 tyrosine and 800 serine/threonine phosphorylation sites in vivo. This study showed that oncogenic FLT3 regulates proteins involving diverse cellular processes and affects multiple signaling pathways in human leukemia that we previously appreciated, such as Fc epsilon RI-mediated signaling, BCR, and CD40 signaling pathways. It provides a valuable resource for investigation of oncogenic FLT3 signaling in human leukemia.
Published Version: doi:10.1371/journal.pone.0019169
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084268/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:5089334

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters