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… 
Modulation of l-α-lysophosphatidylinositol/GPR55 MAP kinase signalling by CB2 receptor agonists: identifying novel GPR55 inhibitors
TLDR
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.
Peptide targeting of lysophosphatidylinositol-sensing GPR55 for osteoclastogenesis tuning
TLDR
The data indicate that GPR55 represents a target for development of novel therapeutic approaches for treatment of pathological conditions caused by osteoclast-exacerbated bone degradation, such as in osteoporosis or during establishment of bone metastases.
Modulation of l-α-Lysophosphatidylinositol/GPR55 Mitogen-activated Protein Kinase (MAPK) Signaling by Cannabinoids*
TLDR
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.
Spatial regulation of GPR64/ADGRG2 signaling by β‐arrestins and GPCR kinases
TLDR
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
TLDR
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.
The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation
TLDR
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
TLDR
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.
A Selective Antagonist Reveals a Potential Role of G Protein–Coupled Receptor 55 in Platelet and Endothelial Cell Function
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
TLDR
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.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 32 REFERENCES
Identification of GPR55 as a lysophosphatidylinositol receptor.
Integrin clustering enables anandamide-induced Ca2+ signaling in endothelial cells via GPR55 by protection against CB1-receptor-triggered repression
TLDR
Data demonstrate that the physiological effects of anandamide on endothelial cells depend on the status of integrin clustering, and that once integrins are clustered, CB1R splits from Integrins and Syk cannot further inhibit GPR55-triggered signaling.
Ligand‐induced down‐regulation of the cannabinoid 1 receptor is mediated by the G‐protein‐coupled receptor‐associated sorting protein GASP1
  • L. Martini, M. Waldhoer, J. Whistler
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2007
TLDR
Treatment with cannabinoid agonists results in CB1R degradation after endocytosis and that the G‐protein‐coupled receptor‐associated sorting protein GASP1 plays a major role in the postendocytic sorting process, which may identify a molecular mechanism underlying tolerance and receptor down‐regulation after long‐term use of cannabinoids.
Gα12/13- and Rho-Dependent Activation of Phospholipase C-ϵ by Lysophosphatidic Acid and Thrombin Receptors
TLDR
These studies illustrate that specific LPA and thrombin receptors promote inositol lipid signaling via activation of Gα12/13 and Rho.
GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current
TLDR
GPR55 is established as a cannabinoid receptor with signaling distinct from CB1 and CB2, and its signaling pathway is found to involve Gq, G12, RhoA, actin, phospholipase C, and calcium release from IP3R-gated stores.
Galpha12/13- and rho-dependent activation of phospholipase C-epsilon by lysophosphatidic acid and thrombin receptors.
TLDR
These studies illustrate that specific LPA and thrombin receptors promote inositol lipid signaling via activation of Galpha(12/13) and Rho.
Modulation of NFAT‐dependent gene expression by the RhoA signaling pathway in T cells
TLDR
RhoA is able to inhibit HIV‐1 gene expression through the NFAT‐binding site in the HIV long‐terminal repeat and activation of RhoA can modulateIL‐2 gene expression by inhibiting the transcriptional activity of NFAT and chromatin structure at the IL‐2 promoter during T cell activation.
Novel cannabinoid receptors
  • A. Brown
  • Biology, Chemistry
    British journal of pharmacology
  • 2007
TLDR
An introduction to non‐CB1/CB2 pharmacology is presented, information on GPR55 and GPR119 currently available is summarized, and their phylogenetic origin is considered, to consider what aspects of non‐ CB1/ CB2 Pharmacology, if any, they help explain.
...
1
2
3
4
...