title: Phosphorylation of CREB in axon-induced Schwann cell proliferation.
abstract: Axonal contact regulates Schwann cell (SC) proliferation during development. However, the intracellular signal transduction pathways involved in the axon-induced proliferation of SC have not been described. We have previously shown that SC proliferation induced by axolemma-enriched fractions (AEF) is accompanied by increased expression of cyclic AMP-responsive element binding protein, CREB. We now report the AEF and dorsal root ganglion neuritic-induced signal transduction pathway(s) which regulate the phosphorylation of CREB that correlate with the SC proliferative response. The phosphorylated form of CREB was significantly increased after 16 hr of axonal stimulation, continued to increase for 48 hr, and subsequently decreased as monitored by immunocytochemistry and Western blot analysis. Treatment with protein kinase A (PKA) inhibitor, H89, completely abolished both the CREB activation and SC proliferation. In contrast, treatment with protein kinase C (PKC) inhibitor (bisindolylmaleimide) inhibited AEF-induced SC proliferation, but did not immediately affect CREB phosphorylation. These data are consistent with the view that PKA and PKC pathways are essential for AEF-induced SC proliferation. Since PKC can influence SC proliferation without initially affecting CREB phosphorylation, PKC may regulate SC proliferation at pathways distal to the immediate CREB activation.
authors.affiliation: Mental Retardation Research Center, Department of Neurobiology, University of California School of Medicine, Los Angeles, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Badache
authors.forename: G H
authors.initials: GH
authors.lastname: DeVries
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008301:Maleimides / Q000494:pharmacology; D016501:Neurites / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology* / Q000502:physiology*; D012584:Sciatic Nerve / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction; D013449:Sulfonamides; D013997:Time Factors
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D008301:Maleimides; D009687:Nuclear Proteins; D013449:Sulfonamides; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C088060:bisindolylmaleimide