The GPR55 ligand L‐α‐lysophosphatidylinositol promotes RhoA‐dependent Ca2+ signaling and NFAT activation

@article{Henstidge2009TheGL,
  title={The GPR55 ligand L‐$\alpha$‐lysophosphatidylinositol promotes RhoA‐dependent Ca2+ signaling and NFAT activation},
  author={Christopher M. Henstidge and Nariman Balenga and Lesley Ann Ford and Ruth Alexandra Ross and Maria Waldhoer and Andrew J. Irving},
  journal={The FASEB Journal},
  year={2009},
  volume={23},
  pages={183 - 193}
}
The endogenous phospholipid l‐α‐lyso‐phosphatidylinositol (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… 
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This structure-activity-relationship study has identified novel ligands which act both as CB2 receptor agonists and GPR55 modulators and related compounds that lack GPR 55 activity.
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The results suggest that this receptor may be responsible for some of the antinociceptive actions of certain CB2 receptor ligands, and suggest that the CB2 ligand GW405833 behaves as a partial agonist of GPR55 alone and enhances LPI signaling.
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Data suggest that NTF not only shields the tethered agonist to prevent G protein signaling but also confers a conformation that inhibits the interaction with β‐arrestins and the consequent endocytosis and sustained signaling from endosomes.
l‐α‐Lysophosphatidylinositol (LPI) aggravates myocardial ischemia/reperfusion injury via a GPR55/ROCK‐dependent pathway
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Raised levels of LPI in the vicinity of a developing infarct may worsen the outcome of AMI, and activation of the Rho kinase/ROCK/p38 MAPK pathway is responsible for LPI‐induced extension of I/R injury.
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A role of LPI and its receptor GPR55 in cancer cells in activating an autocrine loop that regulates cell proliferation and anchorage-independent growth is demonstrated.
BRET analysis reveals interaction between the lysophosphatidic acid receptor LPA2 and the lysophosphatidylinositol receptor GPR55 in live cells
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It is found that LPA2 and GPR55 interact in live cells and co‐activation of receptors synergistically triggered further decline in the cAMP level, promoted cell proliferation, and increased the expression of cancer progression‐related genes, suggesting that physical and functional crosstalk between LPA 2 and GRR55 is involved in cancer progression.
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TLDR
CID16020046 concentration dependently inhibited LPI-induced activation of nuclear factor of activated T-cells, nuclear factor κ of activated B cells and serum response element, translocation of NFAT and NF-κB, and GPR55 internalization, suggesting a novel role for GPR 55 in platelet and endothelial cell function.
GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils
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It is shown that GPR55 is expressed in human blood neutrophils and its activation augments the migratory response towards the CB2R agonist 2-arachidonoylglycerol (2-AG), whilst inhibiting the degranulation and reactive oxygen species (ROS) production.
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