Targeted expression of RALT in mouse skin inhibits epidermal growth factor receptor signalling and generates a Waved-like phenotype.
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.
Ballarò
Costanza
C
Istituto di Biologia Cellulare, CNR, Monterotondo, Italy.
Ceccarelli
Sara
S
Tiveron
Cecilia
C
Tatangelo
Laura
L
Salvatore
Anna Maria
AM
Segatto
Oreste
O
Alemà
Stefano
S
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
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