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Targeted expression of RALT in mouse skin inhibits epidermal growth factor receptor signalling and generates a Waved‐like phenotype
Author(s) -
Ballarò Costanza,
Ceccarelli Sara,
Tiveron Cecilia,
Tatangelo Laura,
Salvatore Anna Maria,
Segatto Oreste,
Alemà Stefano
Publication year - 2005
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400458
Subject(s) - phenotype , epidermal growth factor receptor , microbiology and biotechnology , biology , signalling , receptor , cancer research , genetics , gene
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.