Wnt信号通路
干瘪的
衣冠不整
生物
葛兰素史克-3
信号转导
细胞生物学
LRP5
LRP6型
连环蛋白
GSK3B公司
WNT3A型
癌症研究
作者
Renée van Amerongen,Martijn C. Nawijn,J-P Lambooij,Natalie Proost,Jos Jonkers,Anton Berns
出处
期刊:Oncogene
[Springer Nature]
日期:2009-10-05
卷期号:29 (1): 93-104
被引量:37
摘要
Wnt-signal transduction is critical for development and tissue homeostasis in a wide range of animal species and is frequently deregulated in human cancers. Members of the Frat/GBP family of glycogen synthase kinase 3beta (Gsk3b)-binding oncoproteins are recognized as potent activators of the Wnt/beta-catenin pathway in vertebrates. Here, we reveal a novel, Gsk3b-independent function of Frat converging on the activation of JNK and AP-1. Both these have been used as readouts for the noncanonical Frizzled/PCP pathway, which controls polarized cell movements and the establishment of tissue polarity. We find that Frat synergizes with Diversin, the mammalian homolog of the Drosophila PCP protein diego, in the activation of JNK/AP-1 signaling. Importantly, Frat mutants deficient for binding to Gsk3b retain oncogenic activity in vivo, suggesting that Wnt/beta-catenin-independent events contribute to Frat-induced malignant transformation. The observed activities of Frat are reminiscent of the dual function of Dishevelled in the Wnt/beta-catenin and Frizzled/PCP pathways and suggest that Frat may also function to bridge canonical and noncanonical Wnt pathways.
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