Mitogenic signaling by lysophosphatidic acid (LPA) involves Gα12

doi:10.1038/sj.onc.1208665

科研成果详情

题名	Mitogenic signaling by lysophosphatidic acid (LPA) involves Gα12
作者	Radhika，V.; Ha，Ji Hee; Jayaraman，Muralidharan; Tsim，Siu Tai; Dhanasekaran，N.
发表日期	2005-06-30
发表期刊	Oncogene
ISSN/eISSN	0950-9232
卷号	24 期号:28 页码:4597-4603
摘要	Lysophosphatidic acid (LPA), a major G protein coupled receptor (GPCR)-activating ligand present in serum, elicits growth factor like responses by stimulating specific GPCRs coupled to heterotrimeric G proteins such as G, G, and G. Previous studies have shown that the overexpression of wild-type Gα (Gα WT) results in the oncogenic transformation of NIH3T3 cells (GαWT-NIH3T3) in a serum-dependent manner. Based on the potent growth-stimulating activity of LPA and the presence of LPA and LPA-like molecules in the serum, we hypothesized that the serum-dependent neoplastic transformation of GαWT-NIH3T3 cells was mediated by the stimulation of LPA-receptors (LPARs) by LPA in the serum. In the present study, using guanine nucleotide exchange assay and GST-TPR binding assay, we show that the treatment of GαWT-NIH3T3 with 2 μM LPA leads to the activation of Gα. Stimulation of these cells with LPA promotes JNK-activation, a critical component of Gα-response and cell proliferation. We also show that LPA can substitute for serum in stimulating JNK-activity, DNA synthesis, and proliferation of GαWT-NIH3T3 cells. LPA-mediated proliferative response in NIH3T3 cells involves Gα, but not the closely related Gα. Pretreatment of GαWT-NIH3T3 cells with suramin (100 μM), a receptor-uncoupling agent, inhibited LPA-stimulated proliferation of these cells by 55% demonstrating the signal coupling between cell surface LPAR and Gα in the neoplastic proliferation of NIH3T3 cells. As LPA and LPAR mediated mitogenic pathways have been shown to play a major role in tumor genesis and progression, a mechanistic understanding of the signal coupling between LPAR, Gα, and the downstream effectors is likely to unravel additional targets for novel cancer chemotherapies. © 2005 Nature Publishing Group. All rights reserved.
关键词	Cell-proliferation G protein Gα13 LPA Oncogene Transformation
DOI	10.1038/sj.onc.1208665
URL	查看来源
语种	英语English
Scopus入藏号	2-s2.0-22744444166
引用统计	被引频次：29[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://repository.uic.edu.cn/handle/39GCC9TT/11702
专题	个人在本单位外知识产出
通讯作者	Dhanasekaran，N.
作者单位	Fels Institute for Cancer Research and Molecular Biology,Temple University School Medicine,Philadelphia, PA 19140,United States
推荐引用方式 GB/T 7714	Radhika，V.,Ha，Ji Hee,Jayaraman，Muralidharanet al. Mitogenic signaling by lysophosphatidic acid (LPA) involves Gα12[J]. Oncogene, 2005, 24(28): 4597-4603.
APA	Radhika，V., Ha，Ji Hee, Jayaraman，Muralidharan, Tsim，Siu Tai, & Dhanasekaran，N. (2005). Mitogenic signaling by lysophosphatidic acid (LPA) involves Gα12. Oncogene, 24(28), 4597-4603.
MLA	Radhika，V.,et al."Mitogenic signaling by lysophosphatidic acid (LPA) involves Gα12". Oncogene 24.28(2005): 4597-4603.