title: Targeted expression of RALT in mouse skin inhibits epidermal growth factor receptor signalling and generates a Waved-like phenotype.
abstract: Although it has been clearly established that negative feedback loops have a fundamental role in the regulation of epidermal growth factor receptor (EGFR) signalling in flies, their role in the regulation of mammalian EGFR has been inferred only recently from in vitro studies. Here, we report on the forced expression of RALT/MIG-6, a negative feedback regulator of ErbB receptors, in mouse skin. A RALT transgene driven by the K14 promoter generated a dose-dependent phenotype resembling that caused by hypomorphic and antimorphic Egfr alleles-that is, wavy coat, curly whiskers and open eyes at birth. Ex vivo keratinocytes from K14-RALT mice showed reduced biochemical and biological responses when stimulated by ErbB ligands. Conversely, knockdown of RALT by RNA interference enhanced ErbB mitogenic signalling. Thus, RALT behaves as a suppressor of EGFR signalling in mouse skin.
authors: Istituto di Biologia Cellulare, CNR, Monterotondo, Italy.
authors: Costanza
authors: C
authors: Ballarò
authors: Sara
authors: S
authors: Ceccarelli
authors: Cecilia
authors: C
authors: Tiveron
authors: Laura
authors: L
authors: Tatangelo
authors: Anna Maria
authors: AM
authors: Salvatore
authors: Oreste
authors: O
authors: Segatto
authors: Stefano
authors: S
authors: Alemà
mesh_terms: D000483:Alleles; D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006197:Hair / Q000473:pathology*; D006579:Heterozygote; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D018739:Oncogene Proteins v-erbB / Q000378:metabolism; D016366:Open Reading Frames; D010641:Phenotype; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism*; D013997:Time Factors; D019076:Transgenes; D014738:Vibrissae
chemical_list: C475819:Errfi1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D018739:Oncogene Proteins v-erbB; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D001973:Bromodeoxyuridine