Ceramide 1-phosphate (C1P) promotes cell migration Involvement of a specific C1P receptor.
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 G(i) 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.
Granado
María H
MH
Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain.
Gangoiti
Patricia
P
Ouro
Alberto
A
Arana
Lide
L
González
Monika
M
Trueba
Miguel
M
Gómez-Muñoz
Antonio
A
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002518:Ceramides / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D002518:Ceramides; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D043562:Receptors, G-Protein-Coupled; C065576:ceramide 1-phosphate; C539974:ceramide 1-phosphate receptor, mouse; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases