Acyl-lysophosphatidic acid (acyl-LPA), cyclic-phosphatidic acid (cyclic-PA) and plasmalogen-glycerophosphate (alkenyl-GP) are naturally occurring lipid mediators that belong to the acidic phospholipid autacoid (APA) family. Acyl-LPA elicits diverse biological effects via the activation of G protein-coupled receptors in a variety of cell types. Heterologous desensitization patterns were established between the three APA's, by monitoring changes in intracellular Ca2+ in Xenopus oocytes and NIH3T3 fibroblasts, to determine if these lipids activate the same, or different receptors. AcylLPA cross-desensitized both the alkenyl-GP and cyclic-PA responses. Alkenyl-GP cross-desensitized the cyclic-PA response, but only partially desensitized the acylLPA response. Cyclic-PA only partially desensitized the acyl-LPA and alkenyl-GP responses. Acyl-LPA and alkenyl-GP decreased cAMP in a PTX-sensitive manner, whereas, cyclic-PA caused an increase. Acyl-LPA and alkenyl-GP both stimulated the activity of MAP kinases Erk1/2 and JNK, whereas, cyclic-PA did not. Acyl-LPA and alkenyl-GP both induced proliferation, whereas cyclic-PA was anti-proliferative. All three APA's induced the formation of stress fibers in NIH3T3 fibroblasts. We conclude that subsets of APA receptors exists, which distinguish between cyclic-PA and alkenyl-GP, but are all activated by acyl-LPA. Based on the differences in ligand specificity and signaling properties elicited by the APA's, we introduce a classification for three APA receptor subtypes. Supported by NSF-IBN-9722969, NAHA and LXR.
|Publication status||Published - Dec 1 1998|
ASJC Scopus subject areas
- Molecular Biology