Lysophosphatidic acid (LPA) and lysophosphatidylinositol bind to the G protein-coupled receptors (GPCRs) LPA and GPR55, respectively. LPA2 , a type 2 LPA receptor, and GPR55 are highly expressed in colon cancer and involved in cancer progression. However, crosstalk between the two receptors and potential effects on cellular physiology are not fully understood. Here, using BRET analysis, we found that LPA2 and GPR55 interact in live cells. In the presence of both receptors, LPA2 and/or GPR55 activation facilitated co-internalization, and activation of GPR55, uncoupled with Gαi , induced reduction of intracellular cAMP. Notably, 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 LPA2 and GRR55 is involved in cancer progression.
Keywords: bioluminescence resonance energy transfer technique; cAMP; crosstalk; hypoxia-inducible factor 1α.
© 2021 Federation of European Biochemical Societies.