한빛사논문
- 조회3,498
Abstract
![{dagger}](\"http://www.sciencemag.org/math/link//dagger.gif\")
The canonical Wnt-β-catenin signaling pathway is initiated by
inducing phosphorylation of one of the Wnt receptors, low-density
lipoprotein receptor-related protein 6 (LRP6), at threonine residue
1479 (Thr1479) and serine residue 1490 (Ser1490).
By screening a human kinase small interfering RNA library, we
identified phosphatidylinositol 4-kinase type II ![{alpha}](\"http://www.sciencemag.org/math/alpha.gif\")
and phosphatidylinositol-4-phosphate
5-kinase type I (PIP5KI) as required for Wnt3a-induced LRP6
phosphorylation at Ser1490 in mammalian cells and
confirmed that these kinases are important for Wnt signaling in
Xenopus embryos. Wnt3a stimulates the formation of
phosphatidylinositol 4,5-bisphosphates [PtdIns (4,5)P2]
through frizzled and dishevelled, the latter of which directly
interacted with and activated PIP5KI. In turn, PtdIns
(4,5)P2 regulated phosphorylation of LRP6 at
Thr1479 and Ser1490. Therefore, our study reveals a
signaling mechanism for Wnt to regulate LRP6 phosphorylation.
1 Department of Pharmacology, Yale University School
of Medicine, New Haven, CT 06510, USA.
2 Department of
Developmental and Regenerative Biology, Mount Sinai School of Medicine, New
York, NY 10029, USA.
3 State Key Laboratory of Molecular Biology
and Center of Cell Signaling, Institute of Biochemistry and Cell Biology,
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,
Shanghai 200031, China.
4 Department of Cell Biology and Howard
Hughes Medical Institute, Yale University School of Medicine, New Haven, CT
06510, USA.
5 Department of Medicine, University of Pennsylvania,
Philadelphia, PA 19104, USA.
6 Cell Signaling Technology, Danvers,
MA 01923, USA.
* These authors contribute equally to this work.
![{dagger}](\"http://www.sciencemag.org/math/dagger.gif\")
To whom
correspondence should be addressed.
논문정보
- Research article
- 2008년 09월 (BRIC 등록일 )
- 국외 연구진
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