title: Synergism between temporally distinct growth factors: bFGF, insulin and lens cell differentiation.
abstract: Fibroblast growth factors (FGFs) are the only known factors that can induce differentiation of the mammalian lens epithelial cell, while insulin acts only as a mitogen, not as a morphogen. We show here that insulin enhances expression of the alphaA-crystallin gene in lens epithelial cells and induces the synthesis of lens fibre cell specific betaB2- and gamma-crystallins in early differentiated fibre cells. Different signal transduction pathways are required for bFGF or insulin maintained fibre cell differentiation. A 15 min preincubation with bFGF was sufficient for the lens epithelial cells to become competent to undergo insulin maintained differentiation. The phorbol ester TPA could replace bFGF. The bFGF instructed competence to differentiate decays with a half-life of about 30 h. Hence, bFGF and insulin can act in concert to produce a differentiated phenotype even when they are not present simultaneously.
authors.affiliation: Department of Molecular Biology and Cell Biology, University of Nijmegen, The Netherlands.
authors.forename: W P
authors.initials: WP
authors.lastname: Leenders
authors.forename: S T
authors.initials: ST
authors.lastname: van Genesen
authors.forename: J G
authors.initials: JG
authors.lastname: Schoenmakers
authors.forename: E J
authors.initials: EJ
authors.lastname: van Zoelen
authors.forename: N H
authors.initials: NH
authors.lastname: Lubsen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007908:Lens, Crystalline / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D007328:Insulin; D016222:Fibroblast Growth Factor 2; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate