Lysophospholipids--Receptor Revelations

  title={Lysophospholipids--Receptor Revelations},
  author={Timothy Hla and Menq Jer Lee and Nicolas Ancellin and Jihye Paik and Michael J. Kluk},
  pages={1875 - 1878}
Upon cell activation, membrane phospholipids are metabolized into potent lysophospholipid (LP) mediators, such as sphingosine 1-phosphate and lysophosphatidic acid. LPs fulfill signaling roles in organisms as diverse as yeast and humans. The recent discovery of G protein–coupled receptors for LPs in higher eukaryotes, and their involvement in regulating diverse processes such as angiogenesis, cardiac development, neuronal survival, and immunity, has stimulated growing interest in these lipid… 

Role of Lysophospholipids in Cell Growth and Survival

Evidence is accumulating that most cellular responses to LPA and S1P are mediated through activation of their cognate G protein-coupled receptors (GPCR), which allow activation of a variety of signal transduction pathways that are integrated to trigger diverse cellular responses.

Modulators of lysophosphatidic acid signalling

Based on the action of LPA on molecular targets in different human pathologies, both receptor-selective agonists and antagonists are sought as potential clinical agents.

Sphingosine-1-phosphate: an enigmatic signalling lipid

The evolutionarily conserved actions of the sphingolipid metabolite, sphingosine-1-phosphate (S1P), in yeast, plants and mammals have shown that it has important functions. In higher eukaryotes, S1P

The emerging role of lysophosphatidic acid in cancer

Mechanisms by which LPA production or action could be modulated for cancer therapy are indicated.

Sphingosine-1-phosphate receptors: biology and therapeutic potential in kidney disease.

This review summarizes current knowledge on the biology of S1P and S1PRs that forms the basis for future drug development and the treatment of kidney disease.

Sphingosine-1-Phosphate and the Regulation of Immune Cell Trafficking

Pharmacological and genetic experiments have clearly established the SIP-SIP receptor system as a dominant regulatory axis for the trafficking of lymphocytes and Manipulating this regulatory axis might lead to the development of therapies that target immune system dysfunctions.

Sphingosine 1-phosphate as a novel immune regulator of dendritic cells

The role played by S1P on the DC system and its effects in immune-related pathological states are focused on.

Regulation of macrophage function by sphingosine-1-phosphate.




Lysophosphatidylcholine as a Ligand for the Immunoregulatory Receptor G2A

It is shown that LPC is a high-affinity ligand for G2A, a lymphocyte-expressed G protein–coupled receptor whose genetic ablation results in the development of autoimmunity.

Diversity of cellular receptors and functions for the lysophospholipid growth factors lysophosphatidic acid and sphingosine 1‐phosphate

  • E. GoetzlS. An
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1998
Many of the cellular effects of LPA and S1P are attributable to modifications in the content and/or activity of a major functional protein, including induction of cellular proliferation, alterations in differentiation and survival, and suppression of apoptosis.

Sphingosine 1-phosphate receptors.

  • T. Hla
  • Biology
    Prostaglandins & other lipid mediators
  • 2001

Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1.

Overexpression of EDG-1 induced exaggerated cell-cell aggregation, enhanced expression of cadherins, and formation of well-developed adherens junctions in a manner dependent on SPP and the small guanine nucleotide binding protein Rho.

Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1

Sphingosylphosphorylcholine is shown to be a high-affinity ligand for an orphan receptor, ovarian cancer G-protein-coupled receptor 1 (OGR1), and causes internalization of OGR1 in a structurally specific manner.

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

GPR4 is a receptor with high affinity to SPC and low affinity to LPC, and that multiple cellular functions can be transduced via this receptor, suggesting the involvement of a Gi-heterotrimeric G protein.

Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation.

The data reveal Edg-1 to be the first G protein-coupled receptor required for blood vessel formation and show that sphingolipid signaling is essential during mammalian development.

Prostaglandins and leukotrienes: advances in eicosanoid biology.

  • C. Funk
  • Biology, Chemistry
  • 2001
Important insights into the mechanisms of inflammatory responses, pain, and fever have been gleaned from the current understanding of eicosanoid biology.

Role of the Sphingosine-1-Phosphate Receptor EDG-1 in PDGF-Induced Cell Motility

A role for receptor cross-communication in which activation of a GPCR by a receptor tyrosine kinase is critical for cell motility is revealed.

Schwann cell survival mediated by the signaling phospholipid lysophosphatidic acid.

  • J. WeinerJ. Chun
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
It is reported that LPA (>/=10 nM) is a potent survival factor for cultured neonatal SCs, with survival activity equaling the maximal effect of neuregulin, the major peptide SC survival factor.