| Title | Mitogenic signaling by lysophosphatidic acid (LPA) involves Gα12 |
| Creator | |
| Date Issued | 2005-06-30 |
| Source Publication | Oncogene
 |
| ISSN | 0950-9232 |
| Volume | 24Issue:28Pages:4597-4603 |
| Abstract | 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. |
| Keyword | Cell-proliferation G protein Gα13 LPA Oncogene Transformation |
| DOI | 10.1038/sj.onc.1208665 |
| URL | View source |
| Language | 英语English |
| Scopus ID | 2-s2.0-22744444166 |
| Citation statistics | |
| Document Type | Journal article |
| Identifier | http://repository.uic.edu.cn/handle/39GCC9TT/11702 |
| Collection | Research outside affiliated institution |
| Corresponding Author | Dhanasekaran，N. |
| Affiliation | Fels Institute for Cancer Research and Molecular Biology,Temple University School Medicine,Philadelphia, PA 19140,United States |
| Recommended Citation 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. |
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