Ceramide 1-phosphate (C1P) promotes cell migration. Involvement of a specific C1P receptor

María H. Granado, Patricia Gangoiti, Alberto Ouro, Lide Arana, Monika González, Miguel Trueba, Antonio Gómez-Muñoz

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

Ceramide 1-phosphate (C1P) is a bioactive sphingolipid that is implicated in the regulation of cell homeostasis and the control of inflammation. It is mitogenic for fibroblasts and macrophages, and has been described as potent inhibitor of apoptosis. Using RAW 264.7 macrophages we have now discovered a new biological activity of C1P: stimulation of cell migration. This novel action can only be observed when C1P is applied exogenously to the cells in culture, and not by increasing the intracellular levels of C1P. This fact led to identify a specific receptor through which C1P stimulates cell migration. The receptor is coupled to Gi proteins and causes phosphorylation of extracellularly regulated kinases 1 and 2, and protein kinase B (also known as Akt) upon ligation with C1P. Inhibition of either of these pathways completely abolished C1P-stimulated macrophage migration. In addition, C1P stimulated the DNA binding activity of nuclear factor kappa B, and blockade of this transcription factor resulted in complete inhibition of macrophage migration. This newly identified receptor could be an important drug target for treatment of illnesses that are associated to inflammatory processes, or to diseases in which cell migration is a major cause of pathology, as it occurs in metastatic tumors.

Original languageEnglish
Pages (from-to)405-412
Number of pages8
JournalCellular Signalling
Volume21
Issue number3
DOIs
StatePublished - 1 Mar 2009
Externally publishedYes

Keywords

  • Ceramide
  • Macrophages
  • Mitogen-activated protein kinases
  • Phosphatidylinositol 3-kinase
  • Protein kinase B
  • Sphingolipids

ASJC Scopus subject areas

  • Cell Biology

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