Subtype-specific differential regulation of Rho family G proteins and cell migration by the Edg family sphingosine-1-phosphate receptors

Biochim Biophys Acta. 2002 May 23;1582(1-3):112-20. doi: 10.1016/s1388-1981(02)00145-2.


One of the striking activities of the Edg family sphingosine-1-phosphate (S1P) receptors includes receptor isotype-specific, bimodal regulatory activity on cell migration. While Edg1 and Edg3 act as typical chemotactic receptors, Edg5 uniquely acts as a chemorepellant receptor. Consistent with this, Edg1 and Edg3, and Edg5 regulate the activity of the Rho family GTPase Rac positively and negatively, respectively. Thus, Edg isotype-specific, differential regulatory activities on Rac seem to be important as mechanisms underlying the bimodal regulation of cell migration by S1P. Edg5-mediated Rac inhibition involves stimulation of Rac-GTPase-activating protein (GAP) activity, rather than inhibition of Rac-guanine nucleotide exchange factor (GEF) activity. Many cell types including vascular smooth muscle and endothelial cells express more than a single S1P receptor isotype. In these cells, it appears that an integration of the Edg isotype-selective, positive and negative signals on cellular Rac activity is a critical determinant for eventual direction of regulation on cell motility by S1P. Physiological and pathological roles for the repulsive activity of Edg5 receptor remain to be clarified.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

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


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