In:
Science, American Association for the Advancement of Science (AAAS), Vol. 321, No. 5894 ( 2008-09-05), p. 1350-1353
Abstract:
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 (Thr 1479 ) and serine residue 1490 (Ser 1490 ). By screening a human kinase small interfering RNA library, we identified phosphatidylinositol 4-kinase type II α and phosphatidylinositol-4-phosphate 5-kinase type I (PIP5KI) as required for Wnt3a-induced LRP6 phosphorylation at Ser 1490 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)P 2 ] through frizzled and dishevelled, the latter of which directly interacted with and activated PIP5KI. In turn, PtdIns (4,5)P 2 regulated phosphorylation of LRP6 at Thr 1479 and Ser 1490 . Therefore, our study reveals a signaling mechanism for Wnt to regulate LRP6 phosphorylation.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.1160741
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2008
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11
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