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Endogenous RGS proteins attenuate Galpha(i)-mediated lysophosphatidic acid signaling pathways in ovarian cancer cells.

Publication ,  Journal Article
Hurst, JH; Henkel, PA; Brown, AL; Hooks, SB
Published in: Cell Signal
February 2008

Lysophosphatidic acid is a bioactive phospholipid that is produced by and stimulates ovarian cancer cells, promoting proliferation, migration, invasion, and survival. Effects of LPA are mediated by cell surface G-protein coupled receptors (GPCRs) that activate multiple heterotrimeric G-proteins. G-proteins are deactivated by Regulator of G-protein Signaling (RGS) proteins. This led us to hypothesize 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 LPA activity in SKOV-3 ovarian cancer cells expressing G(i) subunit constructs that are either insensitive to RGS protein regulation (RGSi) or their RGS wild-type (RGSwt) counterparts. Both forms of the G-protein contained a point mutation rendering them insensitive to inhibition with pertussis toxin, and cells were treated with pertussis toxin prior to experiments to eliminate endogenous G(i/o) signaling. The potency and efficacy of LPA-mediated inhibition of forskolin-stimulated adenylyl cyclase activity was enhanced in cells expressing RGSi G(i) proteins as compared to RGSwt G(i). We further showed that LPA signaling that is subject to RGS regulation terminates much faster than signaling thru RGS insensitive G-proteins. Finally, LPA-stimulated SKOV-3 cell migration, as measured in a wound-induced migration assay, was enhanced in cells expressing Galpha(i2) RGSi as compared to cells expressing Galpha(i2) RGSwt, suggesting that endogenous RGS proteins in ovarian cancer cells normally attenuate this LPA effect. These data establish RGS proteins as novel regulators of LPA signaling in ovarian cancer cells.

Duke Scholars

Published In

Cell Signal

DOI

ISSN

0898-6568

Publication Date

February 2008

Volume

20

Issue

2

Start / End Page

381 / 389

Location

England

Related Subject Headings

  • Wound Healing
  • Signal Transduction
  • RGS Proteins
  • Protein Isoforms
  • Pertussis Toxin
  • Ovarian Neoplasms
  • Mutant Proteins
  • Mutagenesis
  • Lysophospholipids
  • Humans
 

Citation

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Hurst, J. H., Henkel, P. A., Brown, A. L., & Hooks, S. B. (2008). Endogenous RGS proteins attenuate Galpha(i)-mediated lysophosphatidic acid signaling pathways in ovarian cancer cells. Cell Signal, 20(2), 381–389. https://doi.org/10.1016/j.cellsig.2007.10.026
Hurst, Jillian H., Paul A. Henkel, April L. Brown, and Shelley B. Hooks. “Endogenous RGS proteins attenuate Galpha(i)-mediated lysophosphatidic acid signaling pathways in ovarian cancer cells.Cell Signal 20, no. 2 (February 2008): 381–89. https://doi.org/10.1016/j.cellsig.2007.10.026.
Hurst, Jillian H., et al. “Endogenous RGS proteins attenuate Galpha(i)-mediated lysophosphatidic acid signaling pathways in ovarian cancer cells.Cell Signal, vol. 20, no. 2, Feb. 2008, pp. 381–89. Pubmed, doi:10.1016/j.cellsig.2007.10.026.
Hurst JH, Henkel PA, Brown AL, Hooks SB. Endogenous RGS proteins attenuate Galpha(i)-mediated lysophosphatidic acid signaling pathways in ovarian cancer cells. Cell Signal. 2008 Feb;20(2):381–389.
Journal cover image

Published In

Cell Signal

DOI

ISSN

0898-6568

Publication Date

February 2008

Volume

20

Issue

2

Start / End Page

381 / 389

Location

England

Related Subject Headings

  • Wound Healing
  • Signal Transduction
  • RGS Proteins
  • Protein Isoforms
  • Pertussis Toxin
  • Ovarian Neoplasms
  • Mutant Proteins
  • Mutagenesis
  • Lysophospholipids
  • Humans