title: beta-Neuregulin and autocrine mediated survival of Schwann cells requires activity of Ets family transcription factors.
abstract: Members of the Ets transcription factor family function in many biological processes. We show the presence of Ets transcription factors, most prominently Net, in neonatal rat Schwann cells, and demonstrate Ets-dependent transcription under conditions where the cells are exposed to autocrine signals or autocrine signals plus beta-neuregulin. Using the potent MAPK kinase inhibitor U0126 we also confirm that the MAP kinase pathway, an activator of Ets transcription, is involved in beta-neuregulin mediated Schwann cell survival. Furthermore, we find that expression of dominant negative Ets1 (N70-Ets1) inhibits both the beta-neuregulin and autocrine survival of Schwann cells. In contrast, the survival of Schwann cells mediated by lysophosphatidic acid (LPA) is unaffected by expression of a dominant negative Ets molecule. These data demonstrate that distinct autocrine and beta-neuregulin survival signals converge in their requirement for Ets dependent transcription in Schwann cell survival.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, Gower Street, United Kingdom.
authors.forename: David B
authors.initials: DB
authors.lastname: Parkinson
authors.forename: Katrin
authors.initials: K
authors.lastname: Langner
authors.forename: Soheila Sharghi
authors.initials: SS
authors.lastname: Namini
authors.forename: Kristjan R
authors.initials: KR
authors.lastname: Jessen
authors.forename: Rhona
authors.initials: R
authors.lastname: Mirsky
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019898:Autocrine Communication / Q000187:drug effects / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051268:GA-Binding Protein Transcription Factor; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D020890:Neuregulin-1 / Q000378:metabolism*; D010525:Peripheral Nerves / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D051268:GA-Binding Protein Transcription Factor; D008246:Lysophospholipids; D020890:Neuregulin-1; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; C494043:Ets1 protein, rat; C417033:net protein, Drosophila; C117467:neuregulin beta