Sphingosylphosphorylcholine and Lysophosphatidylcholine Are Ligands for the G Protein-coupled Receptor GPR4

Zhu, Kui; Baudhuin, Linnea M.; Hong, Guiying; Williams, Freager S.; Cristina, Kelly L.; Kabarowski, Janusz H.; Witte, Owen N.; Xu, Yan

doi:10.1074/jbc.m008057200

Cited by 224 publications

(175 citation statements)

References 38 publications

Supporting

Mentioning

166

Contrasting

Order By: Relevance

“…The LPA-LPA 2/3 GPCR loop also apparently has the capacity to promote cellular survival, migration and spread of ovarian cancer (Zhu et al, 2001;Xu, 2002;Xu et al, 2003). LPA production and expression of one or more LPA GPCRs also have been documented in other cancers and in some normal physiological responses (Tokumura, 2002;Dolezalova et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Induction of protein growth factor systems in the ovaries of transgenic mice overexpressing human type 2 lysophosphatidic acid G protein-coupled receptor (LPA2)

et al. 2004

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Induction of protein growth factor systems in the ovaries of transgenic mice overexpressing human type 2 lysophosphatidic acid G protein-coupled receptor (LPA2)

et al. 2004

View full text Add to dashboard Cite

“…LPC at low concentrations (Ͻ10 M) induces release of osmolytes in various cells (18,19), but the structural requirement for the lysophospholipids is, in the case of the HeLa cells, strict, and only lysophospholipids with choline as the polar head group and oleic, palmitic, or stearic acid in the sn-1 position are able to elicit taurine release (19). Furthermore, LPC binding receptors have recently been identified (13,46). On the other hand, LPC at high concentrations (Ͼ10 M) induces the release of creatine kinase from cardiomyocytes (5), as well as the release of nucleotides from HeLa cells (19).…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species are important mediators of taurine release from skeletal muscle cells

Ørtenblad

Young

Oksbjerg

et al. 2003

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

The present study illustrates elements of the signal cascades involved in the activation of taurine efflux pathways in myotubes derived from skeletal muscle cells. Exposing primary skeletal muscle cells, loaded with 14C-taurine, to 1) hypotonic media, 2) the phospholipase A2 (PLA2) activator melittin, 3) anoxia, or 4) lysophosphatidyl choline (LPC) causes an increase in 14C-taurine release and a concomitant production of reactive oxygen species (ROS). The antioxidants butulated hydroxy toluene and vitamin E inhibit the taurine efflux after cell swelling, anoxia, and addition of LPC. The muscle cells possess two separate taurine efflux pathways, i.e., a swelling- and melittin-induced pathway that requires 5-lipoxygenase activity for activation and a LPC-induced pathway. The two pathways are distinguished by their opposing sensitivity toward the anion channel blocker DIDS and cholesterol. These data provide evidence for PLA2 products and ROS as key mediators of the signal cascade leading to taurine efflux in muscle.

show abstract

“…The authors demonstrate that OGR1 and GPR4, two GPCRs related by a high degree of sequence identity to G2A, can transduce signals independent of their previously identified ligand, SPC (28). Based on the enhancement of these signals by acidic pH, they proposed that OGR1 and GPR4 are proton-sensing GPCRs.…”

Section: The Chemotactic Effect Of Lpc On Do1110 Cells Does Not Appementioning

confidence: 99%

T cell chemotaxis to lysophosphatidylcholine through the G2A receptor

Radu

Yang

Riedinger

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

183

147

View full text Add to dashboard Cite

G2A is an immunoregulatory G protein-coupled receptor predominantly expressed in lymphocytes and macrophages. Ectopic overexpression studies have implicated G2A as a receptor for the bioactive lysophospholipid, lysophosphatidylcholine (LPC). However, the functional consequences of LPC-G2A interaction at physiological levels of receptor expression, and in a cellular context relevant to its immunological role, remain largely unknown. Here, we show impaired chemotaxis to LPC of a T lymphoid cell line in which G2A expression was chronically down-regulated by RNA interference technology. Rescuing this phenotype by reconstitution of the physiological level of receptor expression further supports a functional connection between LPC-G2A interaction and cellular motility. Overexpression of G2A in the T lymphoid cell line significantly enhanced chemotaxis to LPC. It also modified migration toward the LPC-related molecule, lysophosphatidic acid, indicating the possibility of crosstalk between G2A and endogenous lysophosphatidic acid receptors. The role of G2A in LPCmediated cell migration may be relevant to the autoimmune syndrome associated with genetic inactivation of this G proteincoupled receptor in mice. The experimental system described here can be useful for understanding the structural requirements for LPC recognition by G2A and the signaling pathways regulated by this ligand-receptor pair.

show abstract

Sphingosylphosphorylcholine and Lysophosphatidylcholine Are Ligands for the G Protein-coupled Receptor GPR4

Cited by 224 publications

References 38 publications

Induction of protein growth factor systems in the ovaries of transgenic mice overexpressing human type 2 lysophosphatidic acid G protein-coupled receptor (LPA2)

Induction of protein growth factor systems in the ovaries of transgenic mice overexpressing human type 2 lysophosphatidic acid G protein-coupled receptor (LPA2)

Reactive oxygen species are important mediators of taurine release from skeletal muscle cells

T cell chemotaxis to lysophosphatidylcholine through the G2A receptor

Contact Info

Product

Resources

About