Tandem genomic arrangement of a G protein (Gna15) and G protein‐coupled receptor (s1p4/lpC1/Edg6) gene

Contos, James J. A.; Ye, Xiaoqin; Sah, Valerie P.; Chun, Jerold

doi:10.1016/s0014-5793(02)03409-9

Cited by 15 publications

(11 citation statements)

References 26 publications

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“…These results demonstrate that Sph-1-P-induced, Edg-6/S1P4-mediated cell migration requires the activation of Cdc42. spleen and lung, as indicated by Northern blot analysis (Contos et al 2002). These findings strongly suggest that Edg-6/S1P4 may interact with Gα15 at physiological conditions in lymphocytes.…”

Section: Discussionmentioning

confidence: 54%

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Sphingosine 1‐phosphate promotes cell migration through the activation of Cdc42 in Edg‐6/S1P4‐expressing cells

et al. 2003

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Section: Discussionmentioning

confidence: 54%

“…4). Very recently, it was reported that the Gα15 (Gna15) protein is located in tandem just upstream of Edg‐6/S1P4 on the same chromosome, and that these proteins may be coexpressed in the same tissues, such as spleen and lung, as indicated by Northern blot analysis (Contos et al . 2002).…”

Section: Discussionmentioning

confidence: 99%

Sphingosine 1‐phosphate promotes cell migration through the activation of Cdc42 in Edg‐6/S1P4‐expressing cells

et al. 2003

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“…It was found to encode a high-affinity (K d ϭ 13-63 nM) receptor for S1P and a low-affinity receptor for SPC (83,84) and is also encoded on a single exon [reviewed in (4)]. Its comparatively low amino acid sequence similarity compared to the other highaffinity S1P receptors ( Figure 2) suggested that this receptor could have a distinct, preferred ligand (4,85), and indeed, phytosphingosine 1-phosphate (4D-hydroxysphinganine 1-phosphate) has a 50-fold higher affinity for S1P 4 (at 1.6 nM) compared to S1P itself in at least one assay system (86). Virtually all other analyses on S1P 4 were conducted using S1P as the activating ligand, which could have relevance to reported signaling properties of S1P 4 in some biological settings.…”

Section: Sphingosine 1-phosphate Receptormentioning

confidence: 99%

Lysophospholipid Receptors: Signaling and Biology

Ishii

Fukushima

et al. 2004

Annu. Rev. Biochem.

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713

653

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Lysophospholipids (LPs), such as lysophosphatidic acid and sphingosine 1-phosphate, are membrane-derived bioactive lipid mediators. LPs can affect fundamental cellular functions, which include proliferation, differentiation, survival, migration, adhesion, invasion, and morphogenesis. These functions influence many biological processes that include neurogenesis, angiogenesis, wound healing, immunity, and carcinogenesis. In recent years, identification of multiple cognate G protein-coupled receptors has provided a mechanistic framework for understanding how LPs play such diverse roles. Generation of LP receptor-null animals has allowed rigorous examination of receptor-mediated physiological functions in vivo and has identified new functions for LP receptor signaling. Efforts to develop LP receptor subtype-specific agonists/antagonists are in progress and raise expectations for a growing collection of chemical tools and potential therapeutic compounds. The rapidly expanding literature on the LP receptors is herein reviewed.

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“…The fourth S1P receptor, S1P 4 was found as an orphan GPCR in mouse and human dendritic cells [63], and later shown to be a high-affinity S1P receptor and low-affinity SPC receptor [64,65]. It is located on human chromosome 19q22.1-q22.2 and mouse 13B1, encoding a ~42 kd protein.…”

Section: G Protein Coupled Receptors For Lysophosphatidic Acid (Lpa) mentioning

confidence: 99%

“…S1P 4 acts through G i/o , G 12/13 and perhaps G s . It activates adenylate cyclase, Ca 2+ mobilization, cytoskeletal rearrangements, cell motility, MAPK, PLC, and Rho [51,64,65,68]. It's expression is predominantly within immune compartments including lymph nodes, spleen, and thymus [51,63] The fifth receptor is S1P 5 , isolated as an orphan receptor from rat pheochromocytoma 12 (PC12) cells [69], and later identified based on sequence homology as a high-affinity S1P receptor [70][71][72] (reviewed in [20]).…”

Section: G Protein Coupled Receptors For Lysophosphatidic Acid (Lpa) mentioning

confidence: 99%

Lysophospholipid Receptors as Potential Drug Targets in Tissue Transplantation and Autoimmune Diseases

Chun

Rosen²

2006

CPD

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New therapies directed at ameliorating or altering autoimmune diseases represent an area of significant medical need. Included amongst autoimmune diseases are problems related to transplantation rejection, as well as a number of neurological diseases such as Multiple Sclerosis (MS). A new group of molecular targets that may lead to novel therapies are lysophospholipid (LP) receptors. A large range of biological activities has been attributed to the actions of these simple phospholipids that include well-studied members lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). Documented cellular effects of these lipid molecules encompass growth-factor-like influences on cells, including but not limited to survival, migration, adhesion differentiation, as well as pathophysiological actions associated with cancer. In turn, these cellular effects have roles in developing and adult organ systems such as the nervous system, cardiovascular system, reproductive system and, of relevance here, the immune system. The mechanisms for these actions can be attributed to a growing family of cognate, 7-transmembrane G protein-coupled receptors (GPCRs), with documented validation through studies utilizing pharmacology, molecular genetics and an enlarging repertoire of chemical tools having agonist or antagonist properties. The growing literature on immunological effects of LP receptors, particularly those mediating the effects of S1P, has suggested possible therapeutic roles for this class of receptors. In particular, entry into humans of a non-selective S1P receptor agonist, FTY720, for kidney transplantation and possibly other indications (e.g., Multiple Sclerosis), has raised prospects for efficacious treatment of human diseases based on LP receptor targets. Here we provide a brief introduction to receptor-mediated lysophospholipid signaling and discuss its basic and potential therapeutic roles in autoimmune-related diseases.

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Tandem genomic arrangement of a G protein (Gna15) and G protein‐coupled receptor (s1p₄/lp_C1/Edg6) gene

Abstract: A genomic analysis of the s1p 4 /lp C1

Cited by 15 publications

References 26 publications

Sphingosine 1‐phosphate promotes cell migration through the activation of Cdc42 in Edg‐6/S1P4‐expressing cells

Sphingosine 1‐phosphate promotes cell migration through the activation of Cdc42 in Edg‐6/S1P4‐expressing cells

Lysophospholipid Receptors: Signaling and Biology

Lysophospholipid Receptors as Potential Drug Targets in Tissue Transplantation and Autoimmune Diseases

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