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Endogenous RGS proteins attenuate Gα i ‐mediated Lysophosphatidic Acid signaling pathways in Ovarian Cancer Cells
Author(s) -
Hurst Jillian Heyward,
Brown April L.,
Henkel Paul A.,
Hooks Shelley B.
Publication year - 2008
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.22.1_supplement.907.5
Subject(s) - lysophosphatidic acid , rgs2 , g protein , regulator of g protein signaling , heterotrimeric g protein , g protein coupled receptor , microbiology and biotechnology , adenylyl cyclase , ovarian cancer , signal transduction , gtpase activating protein , cancer cell , biology , gs alpha subunit , gi alpha subunit , autocrine signalling , chemistry , cancer research , receptor , cancer , biochemistry , genetics
Lysophosphatidic acid (LPA) is the predominant growth factor driving the progression of ovarian cancer. Effects of LPA are mediated by cell surface G‐protein coupled receptors (GPCRs) that activate multiple heterotrimeric G‐proteins. G‐proteins are deactivated by Regulators of G‐protein Signaling (RGS) proteins. We hypothesized that RGS proteins may regulate G‐protein signaling pathways initiated by LPA in ovarian cancer cells. To determine the effect of endogenous RGS proteins on LPA signaling in ovarian cancer cells, we compared the activity of LPA in ovarian cancer cells expressing Gi subunit constructs that are either insensitive to RGS protein regulation (RGSi) or their RGS‐sensitive wild‐type (RGSwt) counterparts. LPA‐mediated inhibition of forskolin‐stimulated adenylyl cyclase activity was enhanced in cells expressing RGSi Gi proteins as compared to RGSwt Gi, suggesting that endogenous RGS proteins in ovarian cancer cells normally attenuate signaling by these G‐proteins. The enhanced Gi signaling reflected greater potency, efficacy, and duration of LPA effects in the absence of RGS regulation. Further, LPA‐stimulated ovarian cancer cell migration in a wound‐induced migration assay was enhanced in cells expressing Gai2 RGSi as compared to cells expressing Gai2 RGSwt. These data establish RGS proteins as important regulators of LPA signaling in ovarian cancer cells.