Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G12 family to Rho

Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G12 family to Rho
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DOI:
10.1016/s0014-5793(00)02224-9
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发表时间:
2000-11-24
期刊:
影响因子:
3.5
通讯作者:
Gutkind, JS
Gutkind, JS
中科院分区:
生物学3区
文献类型:
--
作者:
Fukuhara, S;Chikumi, H;Gutkind, JS

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最近在急性髓系白血病中发现了一种与MLL基因编码序列融合的鸟嘌呤核苷酸交换因子,称为白血病相关的Rhogef(LARG)。虽然LARG的功能尚不清楚,但它显示了一些结构域,包括PDZ结构域、LH/RGS结构域和DBL同源/Pleckstrin同源结构域。在这里,我们证明了LARG可以在体内激活Rho。此外,我们提出的证据表明,LARG是一个新的生化途径的组成部分,通过G蛋白偶联受体(GPCRs)和异源三聚体G蛋白刺激依赖于Rho的信号通路。(C)2000年欧洲生化学会联合会。爱思唯尔科学公司出版。版权所有。
A putative guanine nucleotide exchange factor (GEF), termed leukemia-associated RhoGEF (LARG), was recently identified upon fusion to the coding sequence of the MLL gene in acute myeloid leukemia. Although the function of LARG is still unknown, it exhibits a number of structural domains suggestive of a role in signal transduction, including a PDZ domain, a LH/ RGS domain, and a Dbl homology/pleckstrin homology domain. Here, we show that LARG can activate Rho in vivo. Furthermore, we present evidence that LARG is an integral component of a novel biochemical route whereby G protein-coupled receptors (GPCRs) and heterotrimeric G proteins of the Gait family stimulate Rho-dependent signaling pathways. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.