Sphingosine 1-Phosphate Receptor 1 Signaling in Mammalian Cells

We describe how sphingosine 1-phosphate receptor 1 can form a complex with G-protein and β-arrestin, which function together to regulate effector pathways

Mammalian Cells

2017

Scholarcy highlights

  • The bioactive lipid, sphingosine 1-phosphate, is produced by phosphorylation of sphingosine, catalysed by two isoforms of sphingosine kinase, whereas its degradation involves cleavage by S1P lyase to produce-2-hexadecenal and phosphoethanolamine
  • We demonstrated that SB649146 is an inverse agonist, a competitive antagonist
  • We reported that the sphingosine 1-phosphate receptor 1 -Platelet derived growth factor receptor β complex contains constitutively active S1P1 and uses Gi, β-arrestin and PDGFRβ tyrosine kinase activity as multipliers of signal output in response to PDGF
  • We have proposed that SB649146 binds to the low efficacy Gi coupling conformation of S1P1, and reduces the concentration of the high efficacy Gi /β-arrestin S1P1 conformation associated with PDGFRβ by mass action
  • S1P1 activates the Janus activated kinase/signal transducer and activator of transcription 3 pathway via IL-6 thereby enhancing T helper 17 polarisation and worsening neuro-inflammation, which is likely to represent a key mechanism in multiple sclerosis. These findings suggest that plasma-membrane S1P1 regulates Jak-STAT3/IL-6 as this is enhanced in cells where S1P1 is resistant to endocytosis
  • Examples could include the use of modulators to manipulate S1P1 -β-arrestin-G-protein complex, S1P1 -Receptor Tyrosine Kinase complex and HDL-S1P signaling in pathogenic conditions such as auto-immune disease, cardiovascular disease and cancer
  • Examples could include the use of modulators to manipulate sphingosine 1-phosphate receptor 1 -β-arrestin-G-protein complex, S1P1 -Receptor Tyrosine Kinase complex and HDL-sphingosine 1-phosphate signaling in pathogenic conditions such as auto-immune disease, cardiovascular disease and cancer

Need more features? Save interactive summary cards to your Scholarcy Library.