Second cysteine-rich domain of Dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of dishevelled

	Second cysteine-rich domain of Dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of dishevelled
	Li, L; Mao, JH; Sun, L; Liu, WZ; Wu, DQ
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2002
卷号	277 期号:8 页码:5977-5981
通讯作者	Li, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai, Peoples R China.,
英文摘要	Recent evidence suggests that members of the Dickkopf (Dkk) family can directly bind to LDL-related protein (LRP)-6, resulting in inhibition of Wnt-activated signaling. To further characterize the interactions between Dkk and LRP proteins, conditioned media containing individually conserved cysteine-rich domains of Dkk-1 and Dkk-2 were prepared. Although full-length Dkk-1 and Dkk-2 and the second cysteine-rich domains of both Dkk molecules inhibited Wnt-3a-induced activation of lymphoid enhancing factor (LEF)-1, a downstream target of the canonical pathway, we found that the second cysteine-rich domain of Dkk-2 (Dkk-2C2) was able to stimulate the canonical pathway when LRP-6 was ectopically expressed in NIH3T3 cells. This effect of Dkk-2C2 could be blocked by a monoclonal antibody specific to the second YWTD repeat domain of LRP-5/6, suggesting that Dkk-2C2 acts via LRP-6. We also showed that while both Axin and the DIX domain of Dishevelled (Dvl) could inhibit Dkk-2C2-induced activation of LEF-1, the DEP domain of Dvl, which inhibited Wnt-induced activation of LEF-1, failed to inhibit the activation of LEF-1 by Dkk-2C2 or by an activated form of LRP-5, LRPC2. In addition, glycogen synthase kinase-3beta, a potent inhibitor for both Dvl and Writ, also failed to inhibit LRPC2 or Dkk-2C2. Furthermore, knocking-down the expression of Dvl molecules by short interfering RNAs specific to Dvl inhibited Wnt-induced, but not LRPC2-induced, activation of LEF-1. All the evidence indicates that Dkk-2C2 signals through LRP proteins, which does not require Dvl, while Wnt protein may employ both Dvl, presumably through Fz, and LRP to achieve more efficient signal transduction.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	BETA-CATENIN ; RECEPTOR ; PROTEINS ; FAMILY ; TRANSDUCTION ; CANCER ; LEF-1 ; DROSOPHILA ; XENOPUS ; MEMBER
收录类别	SCI
语种	英语
WOS记录号	WOS:000173989200037
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2529]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Li, L,Mao, JH,Sun, L,et al. Second cysteine-rich domain of Dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of dishevelled[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2002,277(8):5977-5981.
APA	Li, L,Mao, JH,Sun, L,Liu, WZ,&Wu, DQ.(2002).Second cysteine-rich domain of Dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of dishevelled.JOURNAL OF BIOLOGICAL CHEMISTRY,277(8),5977-5981.
MLA	Li, L,et al."Second cysteine-rich domain of Dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of dishevelled".JOURNAL OF BIOLOGICAL CHEMISTRY 277.8(2002):5977-5981.