Inhibition of Ca2+ signalling by the sphingosine 1-phosphate receptor S1P1

Dagmar Meyer Zu Heringdorf, Myriam E.M. Vincent, Matthias Lipinski, Kerstin Danneberg, Udo Stropp, De An Wang, Gabor Tigyi, Karl H. Jakobs

Research output: Contribution to journalArticle

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Abstract

The lysophospholipid, sphingosine 1-phosphate (S1P), regulates a multitude of cellular functions by activating specific G protein-coupled receptors (GPCRs) (S1P1-5, plus three newly identified S1P receptors). The Gi-coupled S1P1 receptor inhibits adenylyl cyclase, stimulates mitogen-activated protein kinases (MAP kinases) and cell migration, and is required for blood vessel maturation. Here, we report that S1P1 inhibits Ca2+ signalling in a number of cell types. In HEK-293 cells, which endogenously express S1P1-3, overexpression of S1P1 reduced intracellular free Ca2+ concentration ([Ca2+]i) increases induced by various receptor agonists as well as thapsigargin. The inhibitory Ca2+ signalling of S1P1 was blocked by pertussis toxin (PTX) and the protein kinase C (PKC) inhibitor, Gö6976, and imitated by phorbol ester and overexpression of classical PKC isoforms. Activation of S1P1 stably expressed in RH7777 cells, which endogenously do not express S1P receptors, also inhibited Ca2+ signalling, without mediating Ca2+ mobilization on its own. It is concluded that the widely expressed S1P receptor S1P1 inhibits Ca2+ signalling, most likely via Gi proteins and classical PKC isoforms. Co-expression of S1P1 with S1P3, but not S1P2, reversed the inhibitory effect of S1P1, furthermore suggesting a specific interplay of S1P receptor subtypes usually found within a single cell type.

Original languageEnglish (US)
Pages (from-to)677-687
Number of pages11
JournalCellular Signalling
Volume15
Issue number7
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

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Lysosphingolipid Receptors
Protein Kinase C
Protein Isoforms
Lysophospholipids
Thapsigargin
Protein C Inhibitor
HEK293 Cells
Pertussis Toxin
Phorbol Esters
Protein Kinase Inhibitors
G-Protein-Coupled Receptors
Mitogen-Activated Protein Kinases
Adenylyl Cyclases
Cell Movement
Blood Vessels
Cell Count
Proteins

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Zu Heringdorf, D. M., Vincent, M. E. M., Lipinski, M., Danneberg, K., Stropp, U., Wang, D. A., ... Jakobs, K. H. (2003). Inhibition of Ca2+ signalling by the sphingosine 1-phosphate receptor S1P1. Cellular Signalling, 15(7), 677-687. https://doi.org/10.1016/S0898-6568(03)00011-1

Inhibition of Ca2+ signalling by the sphingosine 1-phosphate receptor S1P1. / Zu Heringdorf, Dagmar Meyer; Vincent, Myriam E.M.; Lipinski, Matthias; Danneberg, Kerstin; Stropp, Udo; Wang, De An; Tigyi, Gabor; Jakobs, Karl H.

In: Cellular Signalling, Vol. 15, No. 7, 01.07.2003, p. 677-687.

Research output: Contribution to journalArticle

Zu Heringdorf, DM, Vincent, MEM, Lipinski, M, Danneberg, K, Stropp, U, Wang, DA, Tigyi, G & Jakobs, KH 2003, 'Inhibition of Ca2+ signalling by the sphingosine 1-phosphate receptor S1P1', Cellular Signalling, vol. 15, no. 7, pp. 677-687. https://doi.org/10.1016/S0898-6568(03)00011-1
Zu Heringdorf DM, Vincent MEM, Lipinski M, Danneberg K, Stropp U, Wang DA et al. Inhibition of Ca2+ signalling by the sphingosine 1-phosphate receptor S1P1. Cellular Signalling. 2003 Jul 1;15(7):677-687. https://doi.org/10.1016/S0898-6568(03)00011-1
Zu Heringdorf, Dagmar Meyer ; Vincent, Myriam E.M. ; Lipinski, Matthias ; Danneberg, Kerstin ; Stropp, Udo ; Wang, De An ; Tigyi, Gabor ; Jakobs, Karl H. / Inhibition of Ca2+ signalling by the sphingosine 1-phosphate receptor S1P1. In: Cellular Signalling. 2003 ; Vol. 15, No. 7. pp. 677-687.
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