title: Negative regulation of EGFR/MAPK pathway by Pumilio in Drosophila melanogaster.
abstract: In Drosophila melanogaster, specification of wing vein cells and sensory organ precursor (SOP) cells, which later give rise to a bristle, requires EGFR signaling. Here, we show that Pumilio (Pum), an RNA-binding translational repressor, negatively regulates EGFR signaling in wing vein and bristle development. We observed that loss of Pum function yielded extra wing veins and additional bristles. Conversely, overexpression of Pum eliminated wing veins and bristles. Heterozygotes for Pum produced no phenotype on their own, but greatly enhanced phenotypes caused by the enhancement of EGFR signaling. Conversely, over-expression of Pum suppressed the effects of ectopic EGFR signaling. Components of the EGFR signaling pathway are encoded by mRNAs that have Nanos Response Element (NRE)-like sequences in their 3'UTRs; NREs are known to bind Pum to confer regulation in other mRNAs. We show that these NRE-like sequences bind Pum and confer repression on a luciferase reporter in heterologous cells. Taken together, our evidence suggests that Pum functions as a negative regulator of EGFR signaling by directly targeting components of the pathway in Drosophila.
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Yongbong-Dong, Gwangju, South Korea.
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Kim
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Sumira
authors.initials: S
authors.lastname: Malik
authors.forename: Wonseok
authors.initials: W
authors.lastname: Son
authors.forename: Ki-Sun
authors.initials: KS
authors.lastname: Kwon
authors.forename: Changsoo
authors.initials: C
authors.lastname: Kim
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018010:Receptors, Invertebrate Peptide / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; D018010:Receptors, Invertebrate Peptide; C074333:pum protein, Drosophila; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases