title: The kinase domain of Drosophila Tribbles is required for turnover of fly C/EBP during cell migration.
abstract: Drosophila Tribbles (Trbl) encodes the founding member of the Trib family of kinase-like proteins that regulate cell migration, proliferation, growth and homeostasis. Trbl was identified in a misexpression screen in the ovary as an antagonist of border cell migration and acts in part by directing turnover of the C/EBP protein encoded by the gene slow border cells (slbo). The ability of mammalian Trib isoforms to promote C/EBP turnover during tissue differentiation indicates that this function is highly conserved. To better understand the role of Trbl in cell migration, we tested specific Trbl antisera, a trbl null allele and Trbl transgenes bearing site-directed mutations. Trbl is expressed at high levels in the nuclei of follicle cell epithelia and is downregulated in delaminating epithelia as expression of Slbo (C/EBP) is upregulated. This complementary pattern of expression during subsequent cell migration is achieved by negative feedback whereby slbo represses Trbl expression and trbl is necessary and sufficient to promote Slbo protein turnover. A series of point mutations that scan the conserved kinase domain of Trbl reveal that the conserved DLK catalytic loop is required for Trbl-Slbo binding and turnover, as well as for interactions between Trbl subunits, suggesting a mechanism of Trbl function.
authors.affiliation: Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110, USA.
authors.forename: Venessa
authors.initials: V
authors.lastname: Masoner
authors.forename: Rahul
authors.initials: R
authors.lastname: Das
authors.forename: Laramie
authors.initials: L
authors.lastname: Pence
authors.forename: Gaurav
authors.initials: G
authors.lastname: Anand
authors.forename: Holly
authors.initials: H
authors.lastname: LaFerriere
authors.forename: Troy
authors.initials: T
authors.lastname: Zars
authors.forename: Samuel
authors.initials: S
authors.lastname: Bouyain
authors.forename: Leonard L
authors.initials: LL
authors.lastname: Dobens
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004330:Drosophila / Q000166:cytology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D025461:Feedback, Physiological; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D009154:Mutation; D009866:Oogenesis / Q000235:genetics; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D019076:Transgenes
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D034741:RNA, Small Interfering; C410505:trbl protein, Drosophila; C077246:slbo protein, Drosophila; D017346:Protein Serine-Threonine Kinases