Intracellular Calcium Release Mediated by Sphingosine Derivatives Generated in Cells

Ghosh, Tarun Kanti; Bian, Junhui; Gill, Donald L.

doi:10.1126/science.2163543

Cited by 383 publications

(206 citation statements)

References 41 publications

Supporting

Mentioning

197

Contrasting

Order By: Relevance

“…Culture of Cells-DDT 1 MF-2 smooth muscle cells derived from hamster vas deferens were cultured in Dulbecco's modified Eagle's medium supplemented with 2.5% calf serum as described previously (21,22); DC-3F Chinese hamster lung fibroblasts were cultured in ␣-modified Eagle's medium supplemented with 5% heat-inactivated fetal bovine serum as described previously (23,24).…”

Section: Methodsmentioning

confidence: 99%

Ca2+ Entry Activated byS-Nitrosylation

Hong

Favre²,

Patterson

et al. 1999

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The coupling between Ca 2؉ pools and store-operated Ca 2؉ entry channels (SOCs) remains an unresolved question. Recently, we revealed that Ca 2؉ entry could be activated in response to S-nitrosylation and that this process was stimulated by Ca 2؉ entry suggested a single entry mechanism. Calyculin A-induced reorganization of the actin cytoskeleton prevented SOC but had no effect on GEA3162-induced Ca 2؉ entry. However, a single entry mechanism could account for both SOC and NO donoractivated entry if the latter reflected direct modification of the entry channel by S-nitrosylation, bypassing the normal coupling process between channels and pools. Small differences between SOC and GEA3162-activated Ba 2؉ entry and sensitivity to blockade by La 3؉ were observed, and in HEK293 cells SOC activity was observed without a response to thiol modification. It is concluded that in some cells, S-nitrosylation modifies an entry mechanism closely related to SOC and/or part of the regulatory machinery for SOC-mediated Ca 2؉ entry.

show abstract

Section: Methodsmentioning

confidence: 99%

Ca2+ Entry Activated byS-Nitrosylation

Hong

Favre²,

Patterson

et al. 1999

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…SPC has been shown to affect several cellular processes (19 -22), and interestingly, it can act as a first and second messenger as well (23,24). The best studied intracellular effect of SPC is the liberation of Ca 2ϩ from the endoplasmic reticulum (25). Suggestions have been made on how the sphingolipid elicits Ca 2ϩ release (15, 26 -28), but its site of action is still unclear.…”

Section: Calmodulin (Cam)mentioning

confidence: 99%

“…-saturated CaM and the CaM-binding domain of RyR1-To investigate the possible functional consequences of the CaM inhibitory effect of SPC, we examined the impact of SPC on interactions between CaM and CaM-binding domains of proteins involved in Ca 2ϩ homeostasis, because the best described function of SPC as a putative second messenger is the liberation of Ca 2ϩ from intracellular stores (25). As SPC has been suggested to be involved in activation of ryanodine receptors (RyRs) (15,26), we started working with the CaMbinding domain (amino acids 3614 -3643) of the skeletal muscle Ca 2ϩ release channel (RyR1) (29).…”

Section: Spc Dissociates the Complex Between Ca 2ϩmentioning

confidence: 99%

Dissociation of Calmodulin-Target Peptide Complexes by the Lipid Mediator Sphingosylphosphorylcholine

Kovács¹,

Tóth²,

Vértessy

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…S1P plays fundamental physiological roles in vascular stabilization (4), heart development (5), lymphocyte homing (6), and cancer angiogenesis (7). S1P elicits its biological effects through the activation of G protein-coupled receptors (GPCR) (8 -10) and through yet undefined intracellular targets (11)(12)(13)(14)(15). The endothelial differentiation gene (EDG) family of GPCR encodes eight highly homologous receptors.…”

Section: Sphingosine 1-phosphate (S1p)mentioning

confidence: 99%

Identification of the Hydrophobic Ligand Binding Pocket of the S1P1 Receptor

Fujiwara

Osborne

Walker

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

Sphingosine 1-phosphate (S1P), a naturally occurring sphingolipid mediator and also a second messenger with growth factor-like actions in almost every cell type, is an endogenous ligand of five G protein-coupled receptors (GPCRs) in the endothelial differentiation gene family. The lack of GPCR crystal structures sets serious limitations to rational drug design and in silico searches for subtype-selective ligands. Here we report on the experimental validation of a computational model of the ligand binding pocket of the S1P 1 GPCR surrounding the aliphatic portion of S1P. The extensive mutagenesis-based validation confirmed 18 residues lining the hydrophobic ligand binding pocket, which, combined with the previously validated three head groupinteracting residues, now complete the mapping of the S1P ligand recognition site. We identified six mutants (L3.43G/ L3.44G, L3.43E/L3.44E, L5.52A, F5.48G, V6.40L, and F6.44G) that maintained wild type [ 32 P]S1P binding with abolished ligand-dependent activation by S1P. These data suggest a role for these amino acids in the conformational transition of S1P 1 to its activated state. Three aromatic mutations (F5.48Y, F6.44G, and W6.48A) result in differential activation, by S1P or SEW2871, indicating that structural differences between the two agonists can partially compensate for differences in the amino acid side chain. The now validated ligand binding pocket provided us with a pharmacophore model, which was used for in silico screening of the NCI, National Institutes of Health, Developmental Therapeutics chemical library, leading to the identification of two novel nonlipid agonists of S1P 1 .Sphingosine 1-phosphate (S1P)3 (see Fig. 1) is a naturally occurring sphingolipid mediator and also a second messenger with growth factor-like actions in almost every cell type (1-3). S1P plays fundamental physiological roles in vascular stabilization (4), heart development (5), lymphocyte homing (6), and cancer angiogenesis (7). S1P elicits its biological effects through the activation of G protein-coupled receptors (GPCR) (8 -10) and through yet undefined intracellular targets (11-15). The endothelial differentiation gene (EDG) family of GPCR encodes eight highly homologous receptors. Five of these receptors, designated S1P 1 -S1P 5 , are specific for S1P, and the other three, LPA 1 -LPA 3 , are specific for the related lysophospholipid mediator lysophosphatidic acid (LPA) (16).FTY-720, an immunosuppressive prodrug presently in phase 3 clinical trials, has attracted a lot of interest due to its effective inhibition of kidney transplant rejection and attenuation of autoimmune diseases, including multiple sclerosis (6,17,18). In vivo, FTY-720 becomes phosphorylated by sphingosine kinase type 2, and FTY-720-P is a high affinity ligand of all EDG family S1P receptors with the exception of S1P 2 (19). In atrial myocytes, FTY-720-P, similarly to S1P (20, 21), activates an inwardly rectifying K ϩ conductance through the activation of the S1P 3 receptor, which in turn elicits unwanted bradyca...

show abstract

Intracellular Calcium Release Mediated by Sphingosine Derivatives Generated in Cells

Cited by 383 publications

References 41 publications

Ca2+ Entry Activated byS-Nitrosylation

Ca2+ Entry Activated byS-Nitrosylation

Dissociation of Calmodulin-Target Peptide Complexes by the Lipid Mediator Sphingosylphosphorylcholine

Identification of the Hydrophobic Ligand Binding Pocket of the S1P1 Receptor

Contact Info

Product

Resources

About