Publication Date:
2008-09-06
Description:
The canonical Wnt-beta-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 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532521/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532521/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pan, Weijun -- Choi, Sun-Cheol -- Wang, He -- Qin, Yuanbo -- Volpicelli-Daley, Laura -- Swan, Laura -- Lucast, Louise -- Khoo, Cynthia -- Zhang, Xiaowu -- Li, Lin -- Abrams, Charles S -- Sokol, Sergei Y -- Wu, Dianqing -- AR051476/AR/NIAMS NIH HHS/ -- CA132317/CA/NCI NIH HHS/ -- DA018343/DA/NIDA NIH HHS/ -- HL080706/HL/NHLBI NIH HHS/ -- NS36251/NS/NINDS NIH HHS/ -- P30 DA018343/DA/NIDA NIH HHS/ -- R01 AR051476/AR/NIAMS NIH HHS/ -- R01 AR051476-01A1/AR/NIAMS NIH HHS/ -- R01 AR051476-02/AR/NIAMS NIH HHS/ -- R01 AR051476-03/AR/NIAMS NIH HHS/ -- R01 CA132317/CA/NCI NIH HHS/ -- R01 CA132317-01A2/CA/NCI NIH HHS/ -- R01 CA139395/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Sep 5;321(5894):1350-3. doi: 10.1126/science.1160741.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18772438" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing/metabolism
;
Animals
;
Axin Protein
;
Cell Line
;
Frizzled Receptors/metabolism
;
Humans
;
LDL-Receptor Related Proteins/*metabolism
;
Low Density Lipoprotein Receptor-Related Protein-6
;
Mice
;
Models, Biological
;
Phosphatidylinositol 4,5-Diphosphate/*metabolism
;
Phosphoproteins/metabolism
;
Phosphorylation
;
Phosphotransferases (Alcohol Group Acceptor)/metabolism
;
RNA, Small Interfering
;
Recombinant Proteins/metabolism
;
Repressor Proteins/metabolism
;
Serine/metabolism
;
Signal Transduction
;
Threonine/metabolism
;
Wnt Proteins/*metabolism
;
Wnt3 Protein
;
Wnt3A Protein
;
Xenopus/embryology
;
Xenopus Proteins
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
