title: Signal transduction mechanisms involved in the proliferation of C6 glioma cells induced by lysophosphatidic acid.
abstract: We studied pathways involved in the proliferation of rat C6 glioma cells induced by lysophosphatidic acid (LPA), a phospholipid with diverse biological functions. LPA induced a dose-responsive proliferation of C6 cells after 48 h. Proliferation was blocked by inhibitors of the sodium/proton exchanger type 1 (NHE1), Rho-associated kinase, the phosphatidylinositol 3-kinase/Akt pathway (PI3K/Akt), protein kinase C (PKC) and extracellular signal regulated kinase kinase (MEK). Phospho-specific antibodies were used to investigate the pathways involved. LPA induced transient (10 min) phosphorylations of ERK 1/2, Akt and the transcription factor CREB. The LPA-induced phosphorylation of ERK 1/2 and CREB was blocked by inhibition of PI3K, PKC and MEK, but that of Akt was only inhibited by wortmannin, the PI3K inhibitor. Inhibition of Rho kinase or NHE1 did not reduce the LPA-induced phosphorylation of ERK, Akt or CREB. The results were compared with the effects of LPA on transduction pathways in other cell types.
authors.affiliation: School of Biomedical Sciences and the Hunter Medical Research Institute, University of Newcastle, 2308, Callaghan, NSW, Australia.
authors.forename: Sirlene R
authors.initials: SR
authors.lastname: Cechin
authors.forename: Peter R
authors.initials: PR
authors.lastname: Dunkley
authors.forename: Richard
authors.initials: R
authors.lastname: Rodnight
mesh_terms: D027682:Cation Transport Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005910:Glioma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D008246:Lysophospholipids; D008565:Membrane Proteins; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D011494:Protein Kinases; C032881:lysophosphatidic acid