Lysophosphatidic acid as a novel cell survival/apoptotic factor.
Lysophosphatidic acid (LPA) activates its cognate G protein-coupled receptors (GPCRs) LPA(1-3) to exert diverse cellular effects, including cell survival and apoptosis. The potent survival effect of LPA on Schwann cells (SCs) is mediated through the pertussis toxin (PTX)-sensitive G(i/o)/phosphoinositide 3-kinase (PI3K)/Akt signaling pathways and possibly enhanced by the activation of PTX-insensitive Rho-dependent pathways. LPA promotes survival of many other cell types mainly through PTX-sensitive G(i/o) proteins. Paradoxically, LPA also induces apoptosis in certain cells, such as myeloid progenitor cells, hippocampal neurons, and PC12 cells, in which the activation of the Rho-dependent pathways and caspase cascades has been implicated. The effects of LPA on both cell survival and apoptosis underscore important roles for this lipid in normal development and pathological processes.
Ye
Xiaoqin
X
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0636, USA.
Ishii
Isao
I
Kingsbury
Marcy A
MA
Chun
Jerold
J
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000502:physiology*; D023461:Myeloid Progenitor Cells; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D012234:Rho Factor / Q000378:metabolism; D012583:Schwann Cells; D015398:Signal Transduction
D020169:Caspases; D019204:GTP-Binding Proteins; D008246:Lysophospholipids; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D012234:Rho Factor; C494918:AKT1 protein, human; C494920:Akt1 protein, rat