Department of Life Science, Kyonggi University, Suwon, Korea.
FEBS Lett. 2021 Jul;595(13):1806-1818. doi: 10.1002/1873-3468.14102. Epub 2021 May 19.
Lysophosphatidic acid (LPA) and lysophosphatidylinositol bind to the G protein-coupled receptors (GPCRs) LPA and GPR55, respectively. LPA , 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 LPA and GPR55 interact in live cells. In the presence of both receptors, LPA and/or GPR55 activation facilitated co-internalization, and activation of GPR55, uncoupled with Gα , 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 LPA and GRR55 is involved in cancer progression.
溶血磷脂酸（LPA）和溶血磷脂酰肌醇分别与 G 蛋白偶联受体（GPCR）LPA 和 GPR55 结合。LPA 是一种 2 型 LPA 受体，在结肠癌中高度表达，并参与癌症进展。然而，这两种受体之间的串扰及其对细胞生理学的潜在影响尚不完全清楚。在这里，我们使用 BRET 分析发现 LPA 和 GPR55 在活细胞中相互作用。在存在这两种受体的情况下，LPA 和/或 GPR55 的激活促进了共内化，并且与 Gα 解偶联的 GPR55 激活诱导细胞内 cAMP 的减少。值得注意的是，受体的共激活协同地触发了 cAMP 水平的进一步下降，促进了细胞增殖，并增加了癌症进展相关基因的表达，这表明 LPA 和 GRR55 之间的物理和功能串扰参与了癌症的进展。
