RRC ID 33719
著者 Enomoto M, Kizawa D, Ohsawa S, Igaki T.
タイトル JNK signaling is converted from anti- to pro-tumor pathway by Ras-mediated switch of Warts activity.
ジャーナル Dev Biol
Abstract The c-Jun N-terminal kinase (JNK) pathway is a dual-functional oncogenic signaling that exerts both anti- and pro-tumor activities. However, the mechanism by which JNK switches its oncogenic roles depending on different cellular contexts has been elusive. Here, using the Drosophila genetics, we show that hyperactive Ras acts as a signaling switch that converts JNK's role from anti- to pro-tumor signaling through the regulation of Hippo signaling activity. In the normal epithelium, JNK signaling antagonizes the Hippo pathway effector Yorkie (Yki) through elevation of Warts activity, thereby suppressing tissue growth. In contrast, in the presence of hyperactive Ras, JNK signaling enhances Yki activation by accumulating F-actin through the activity of the LIM domain protein Ajuba, thereby promoting tissue growth. We also find that the epidermal growth factor receptor (EGFR) signaling uses this Ras-mediated conversion of JNK signaling to promote tissue growth. Our observations suggest that Ras-mediated switch of the JNK pathway from anti- to pro-tumor signaling could play crucial roles in tumorigenesis as well as in normal development.
巻・号 403(2)
ページ 162-71
公開日 2015-7-15
DOI 10.1016/j.ydbio.2015.05.001
PII S0012-1606(15)00249-3
PMID 25967126
MeSH Animals Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / growth & development* Drosophila melanogaster / metabolism* Humans Imaginal Discs / metabolism* Intracellular Signaling Peptides and Proteins / metabolism MAP Kinase Signaling System* Neoplasms / metabolism Nuclear Proteins / metabolism Protein Kinases / genetics Protein Kinases / metabolism* Protein Serine-Threonine Kinases / metabolism Trans-Activators / metabolism YAP-Signaling Proteins ras Proteins / metabolism*
IF 2.896
引用数 33
WOS 分野 DEVELOPMENTAL BIOLOGY
リソース情報
ショウジョウバエ 12072R-1 4005R-2