Document Detail

The G-protein coupled receptor 34(Gpr34) activates Erk and PI3K/Akt pathways and functions as an alternative pathway to mediate p185Bcr-Abl-induced transformation and leukemogenesis.
MedLine Citation:
PMID:  25363403     Owner:  NLM     Status:  Publisher    
Abstract The tyrosine 177 and Src homology 2 domains (SH2) play important roles in linking p185Bcr-Abl to downstream pathways critical for cell growth and survival. However, a mutant p185(Y177FR552L) (p185(YR)), in which the tyrosine 177 and arginine 552 in the SH2 domain were mutated, is still capable of transforming hematopoietic cells in vitro. Transplantation of these cells into syngenic mice also leads to leukemogenesis, albeit with a phenotype distinctive to that produced by the wild-type p185Bcr-Abl(p185(wt))-transformed cells. Here we showthat Gpr34-expression is markedly up-regulated in p185(YR)-transformed cells compared to those transformed by p185(wt). Knockdown of Gpr34 in p185(YR) cells is sufficient to suppress the growth factor-independent proliferation and survival in vitro and attenuate the leukemogenesis in vivo. The Erk and PI3K/Akt pathways are activated in p185(YR) cells and the activation is dependent on Gpr34 expression. These studies identify Gpr34 as an alternative pathway that may mediate p185Bcr-Abl-induced transformation and leukemogenesis. Introduction.
Bo Zuo; Mei Li; Yulan Liu; Kun Li; Shuyun Ma; Meihua Cui; Yazhen Qin; Honghu Zhu; Xiuying Pan; Jingzhu Guo; Zonghan Dai; Weidong Yu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-3
Journal Detail:
Title:  Leukemia & lymphoma     Volume:  -     ISSN:  1029-2403     ISO Abbreviation:  Leuk. Lymphoma     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-3     Completed Date:  -     Revised Date:  2014-11-5    
Medline Journal Info:
Nlm Unique ID:  9007422     Medline TA:  Leuk Lymphoma     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1-41     Citation Subset:  -    
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