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Selective activation of the MAP kinases by LPA in ovarian cancer cells
Author(s) -
Goldsmith Zachariah G.,
Ha Ji Hee,
Dhansekaran Danny N.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a535-c
Subject(s) - mapk/erk pathway , lysophosphatidic acid , kinase , p38 mitogen activated protein kinases , microbiology and biotechnology , mitogen activated protein kinase , phosphorylation , cell growth , autocrine signalling , cancer research , biology , chemistry , receptor , biochemistry
Lysophosphatidic acid (LPA) is a tumor biomarker and crucial growth factor in the pathophysiology of ovarian carcinoma. LPA is produced by malignant ovarian cells, and forms an autocrine loop by stimulating neovascularization, invasion, and cell proliferation via its cognate family of high‐affinity G Protein coupled receptors (GPCRs). However, the mechanisms by which LPA mediates cell proliferation have yet to be fully elucidated. With a view to understand the molecular mechanisms underlying LPA‐mediated cell proliferation and oncogenic growth, we investigated the activation of the MAP kinases (ERK, JNK, and p38) by LPA. Herein we report that LPA activates ERK and JNK in the C272 ovarian carcinoma cell line. Stimulation with 10 ?M LPA induced an increase in the levels of phosphorylated ERK and JNK, but no change in the phosphorylation status of p38, as determined by immunoblot analysis. Levels of phosphorylated JNK and ERK peaked at 10 and 30 minutes of LPA stimulation, respectively. The selective phosphorylation of ERK and JNK correlated with an increase in the activity of these kinases. LPA stimulation induced an increase in the kinase activity of JNK and ERK with no change in p38 MAPK activity, as revealed by solid‐phase and immune‐complex in vitro kinase assays, respectively. As LPA is known to stiumulate mitogenic pathways via the activation of multiple G‐proteins, studies are currently underway to determine the requisite LPAR(s), G‐protein(s), and downstream kinases that mediate cell proliferation by LPA in ovarian cancer cells. (This work was supported by GM49897, Pennsylvania Department of Health Commonwealth Universal Research Enhancement (CURE) Program, and the Temple University School of Medicine MD/PhD Program).