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- Title
The GPR55 ligand L-α-lysophosphatidylinositol promotes RhoA-dependent Ca<sup>2+</sup> signaling and NFAT activation.
- Authors
Henstridge, Christopher M.; Balenga, Nariman A. B.; Ford, Lesley A.; Ross, Ruth A.; Waldhoer, Maria; Irving, Andrew J.
- Abstract
The endogenous phospholipid L-α-lysophosphatidylinositol (LPI) was recently identified as a novel ligand for the orphan G protein-coupled receptor 55 (GPR55). In this study we define the downstream signaling pathways activated by LPI in a human embryonic kidney (HEK) 293 cell line engineered to stably express recombinant human GPR55. We find that treatment with LPI induces marked GPR55 internalization and stimulates a sustained, oscillatory Ca2+ release pathway, which is dependent on Gα13 and requires RhoA activation. We then establish that this signaling cascade leads to the efficient activation of NFAT (nuclear factor of activated T cells) family transcription factors and their nuclear translocation. Analysis of cannabinoid ligand activity at GPR55 revealed no clear effect of the endocannabinoids anandamide and 2-arachidonoylglycerol; however, the classical CB1 antagonist AM251 evoked GPR55-mediated Ca2+ signaling. Thus, LPI is a potent and efficacious ligand at GPR55, which is likely to be a key plasma membrane mediator of LPI-mediated signaling events and changes in gene expression.
- Subjects
LIGANDS (Biochemistry); PHOSPHOLIPIDS; G proteins; RECOMBINANT proteins; CALCIUM; T cells; TRANSCRIPTION factors
- Publication
FASEB Journal, 2009, Vol 23, Issue 1, p183
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.08-108670