Recombinant Human G Protein-Coupled Lysophosphatidic Acid Receptors Mediate Intracellular Calcium Mobilization

Abstract

Mobilization of intracellular Ca2ϩ is a critical cellular response to lysophosphatidic acid (LPA) in many cell types. Recent identification of endothelial differentiation gene (Edg) 2 and Edg4 as subtypes of G protein-coupled receptors for LPA allowed examination of the Ca 2ϩ mobilization mediated specifically by each subtype. To reduce endogenous background levels while enhancing recombinant receptor-specific signals, the aequorin luminescence method was used to quantify cytoplasmic Ca 2ϩ

The platelet-derived-growth-factor receptor, not the epidermal-growth-factor receptor, is used by lysophosphatidic acid to activate p42/44 mitogen-activated protein kinase and to induce prostaglandin G/H synthase-2 in mesangial cells

“…In contrast with many other cells [26], however, release of intracellular calcium mediated by phosphatidylinositol-specific phospholipase C is also sensitive to PTX in mesangial cells [5]. These data are in accordance with the PTX-sensitive calcium mobilization by transfected LPA receptors, especially the Edg2 receptor, recently shown by An et al [27]. Furthermore, activation of PKC by LPA was attributed to G-proteins of the G q family (discussed in [13]).…”

Molecular Cloning and Characterization of a Novel Human G-protein-coupled Receptor, EDG7, for Lysophosphatidic Acid

“…It has been previously demonstrated that LPA-induced Ca 2ϩ mobilization can be transduced through both PTX-sensitive (32) and PTX-insensitive (33-35) G-protein followed by activation of PLC. An et al (36) used TAg-Jurkat T cells transiently transfected with human EDG2 or EDG4 to demonstrate that PTX completely blocks LPAinduced Ca 2ϩ mobilization in EDG2-expressing cells, and partially blocks it in EDG4-expressing cells. They speculated from these data that EDG2 is coupled to PTX-sensitive G i , whereas EDG4 is coupled to both G i and G q (36).…”

Involvement of lipoxygenase in lysophosphatidic acid-stimulated hydrogen peroxide release in human HaCaT keratinocytes

“…It is well known that LPA induces calcium mobilization [23,24]. As shown in Figure 5, LPAstimulated H # O # release was inhibited when cells were incubated with the intracellular calcium-chelator BAPTA-AM.…”