Endogenous lysophosphatidic acid (LPA1) receptor agonists demonstrate ligand bias between calcium and ERK signalling pathways in human lung fibroblasts
Background and Purpose Human lung fibroblasts (HLF) express high levels of the LPA1 receptor, a GPCR that responds to the endogenous lipid mediator, lysophosphatidic acid (LPA). Several molecular species or analogues of LPA exist and have been detected in biological fluids such as serum and plasm...
| Main Authors: | , , |
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| Format: | Article |
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Wiley
2017
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| Online Access: | https://eprints.nottingham.ac.uk/41457/ |
| _version_ | 1848796277668577280 |
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| author | Sattikar, Afrah Dowling, Mark R, Rosethorne, Elizabeth M. |
| author_facet | Sattikar, Afrah Dowling, Mark R, Rosethorne, Elizabeth M. |
| author_sort | Sattikar, Afrah |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Background and Purpose
Human lung fibroblasts (HLF) express high levels of the LPA1 receptor, a GPCR that responds to the endogenous lipid mediator, lysophosphatidic acid (LPA). Several molecular species or analogues of LPA exist and have been detected in biological fluids such as serum and plasma. The most widely expressed of the LPA receptor family is the LPA1 receptor, which predominantly couples to Gq/11, Gi/o and G12/13 proteins. This promiscuity of coupling raises the possibility that some of the LPA analogues may bias the LPA1 receptor towards one signalling pathway over another.
Experimental Approach
Here, we have explored the signalling profiles of a range of LPA analogues in HLF that endogenously express the LPA1 receptor. HLF were treated with LPA analogues and receptor activation monitored via calcium mobilization and ERK phosphorylation.
Key Results
These analyses demonstrated that the 16:0, 17:0, 18:2 and C18:1 LPA analogues appear to exhibit ligand bias between ERK phosphorylation and calcium mobilization when compared with 18:1 LPA, one of the most abundant forms of LPA that has been found in human plasma.
Conclusion and Implications
The importance of LPA as a key signalling molecule is shown by its widespread occurrence in biological fluids and its association with disease conditions such as fibrosis and cancer. These findings have important, as yet unexplored, implications for the (patho-) physiological signalling of the LPA1 receptor, as it may be influenced not only by the concentration of endogenous ligand but the isoform as well. |
| first_indexed | 2025-11-14T19:45:26Z |
| format | Article |
| id | nottingham-41457 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:45:26Z |
| publishDate | 2017 |
| publisher | Wiley |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-414572020-05-04T19:58:48Z https://eprints.nottingham.ac.uk/41457/ Endogenous lysophosphatidic acid (LPA1) receptor agonists demonstrate ligand bias between calcium and ERK signalling pathways in human lung fibroblasts Sattikar, Afrah Dowling, Mark R, Rosethorne, Elizabeth M. Background and Purpose Human lung fibroblasts (HLF) express high levels of the LPA1 receptor, a GPCR that responds to the endogenous lipid mediator, lysophosphatidic acid (LPA). Several molecular species or analogues of LPA exist and have been detected in biological fluids such as serum and plasma. The most widely expressed of the LPA receptor family is the LPA1 receptor, which predominantly couples to Gq/11, Gi/o and G12/13 proteins. This promiscuity of coupling raises the possibility that some of the LPA analogues may bias the LPA1 receptor towards one signalling pathway over another. Experimental Approach Here, we have explored the signalling profiles of a range of LPA analogues in HLF that endogenously express the LPA1 receptor. HLF were treated with LPA analogues and receptor activation monitored via calcium mobilization and ERK phosphorylation. Key Results These analyses demonstrated that the 16:0, 17:0, 18:2 and C18:1 LPA analogues appear to exhibit ligand bias between ERK phosphorylation and calcium mobilization when compared with 18:1 LPA, one of the most abundant forms of LPA that has been found in human plasma. Conclusion and Implications The importance of LPA as a key signalling molecule is shown by its widespread occurrence in biological fluids and its association with disease conditions such as fibrosis and cancer. These findings have important, as yet unexplored, implications for the (patho-) physiological signalling of the LPA1 receptor, as it may be influenced not only by the concentration of endogenous ligand but the isoform as well. Wiley 2017-02 Article PeerReviewed Sattikar, Afrah, Dowling, Mark R, and Rosethorne, Elizabeth M. (2017) Endogenous lysophosphatidic acid (LPA1) receptor agonists demonstrate ligand bias between calcium and ERK signalling pathways in human lung fibroblasts. British Journal of Pharmacology, 174 (3). pp. 227-237. ISSN 1476-5381 http://onlinelibrary.wiley.com/doi/10.1111/bph.13671/full doi:10.1111/bph.13671 doi:10.1111/bph.13671 |
| spellingShingle | Sattikar, Afrah Dowling, Mark R, Rosethorne, Elizabeth M. Endogenous lysophosphatidic acid (LPA1) receptor agonists demonstrate ligand bias between calcium and ERK signalling pathways in human lung fibroblasts |
| title | Endogenous lysophosphatidic acid (LPA1) receptor agonists demonstrate ligand bias between calcium and ERK signalling pathways in human lung fibroblasts |
| title_full | Endogenous lysophosphatidic acid (LPA1) receptor agonists demonstrate ligand bias between calcium and ERK signalling pathways in human lung fibroblasts |
| title_fullStr | Endogenous lysophosphatidic acid (LPA1) receptor agonists demonstrate ligand bias between calcium and ERK signalling pathways in human lung fibroblasts |
| title_full_unstemmed | Endogenous lysophosphatidic acid (LPA1) receptor agonists demonstrate ligand bias between calcium and ERK signalling pathways in human lung fibroblasts |
| title_short | Endogenous lysophosphatidic acid (LPA1) receptor agonists demonstrate ligand bias between calcium and ERK signalling pathways in human lung fibroblasts |
| title_sort | endogenous lysophosphatidic acid (lpa1) receptor agonists demonstrate ligand bias between calcium and erk signalling pathways in human lung fibroblasts |
| url | https://eprints.nottingham.ac.uk/41457/ https://eprints.nottingham.ac.uk/41457/ https://eprints.nottingham.ac.uk/41457/ |