Pathways of transduction engaged by sphingosine 1-phosphate through G protein-coupled receptors

Biochim Biophys Acta. 2002 May 23;1582(1-3):94-9. doi: 10.1016/s1388-1981(02)00142-7.


Pathways of transduction employed by receptors for sphingosine 1-phosphate (S1P) are identified by the nature of second messengers and/or downstream targets regulated and, more formally, by direct assays of heterotrimeric G protein activation. The different methods generally agree. S1P1 couples to members of the Gi family, apparently selectively, although reported pertussis toxin (PTX)-insensitive actions make categorical statements regarding exclusivity difficult. S1P2 and S1P3 couple to members of the Gi, Gq, and G12/13 families. S1P4 couples to Gi and possibly G12/13, while S1P5 couples to Gi and G12/13 but not to Gq. In virtually all circumstances, coupling of S1P receptors to Gi is reflected in PTX-sensitive inhibition of adenylyl cyclase, activation of extracellular-regulated kinases (ERKs), and, depending on the cell, activation of phospholipase C (PLC). Coupling to Gq is reflected in PTX-insensitive activation of phospholipase C. Coupling to G12/13 is reflected in activation of Rho and subsequent activation of serum response factor (SRF). Specific linkages have been verified in almost all instances by receptor-promoted [35S]GTPgammaS/GDP exchange on identified G proteins.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins / physiology
  • GTP-Binding Proteins / physiology*
  • I-kappa B Proteins*
  • Immediate-Early Proteins / physiology
  • Lysophospholipids*
  • NF-KappaB Inhibitor alpha
  • Receptors, Cell Surface / physiology*
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophospholipid
  • Signal Transduction / physiology*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / physiology*


  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Immediate-Early Proteins
  • Lysophospholipids
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophospholipid
  • NF-KappaB Inhibitor alpha
  • sphingosine 1-phosphate
  • GTP-Binding Proteins
  • Sphingosine