Lysophosphatidic acid regulates trafficking of β₂- adrenergic receptors: The Gα₁₃/p115RhoGEF/JNK pathway stimulates receptor internalization

Lysophosphatidic acid is an important lipid ligand regulating many aspects of cell function, including proliferation and migration. Operating via heterotrimeric G proteins to downstream effectors, lysophosphatidic acid was shown to regulate the function and trafficking of the G protein-coupled β₂-adrenergic receptor. C3 exotoxin, expression of dominant negative RhoA, and inhibition of c-Jun N-terminal kinase blocked the ability of lysophosphatidic acid to sequester the β₂-adrenergic receptor, whereas expression of constitutively active Gα₁₃, p115RhoGEF, or RhoA mimicked lysophosphatidic acid (LPA) action, stimulating the internalization of the Gα_s-coupled β₂- adrenergic receptor. This study revealed a novel cross-talk exerted from the LPA/Gα13/p115RhoGEF/RhoA pathway to the β₂-adrenergic receptor/Gα_s/adenylyl cyclase pathway, attenuating the ability of β-adrenergic agonists to act following stimulation of cells by LPA as may occur during β-adrenergic therapy of an inflammatory response.