Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 Phosphorylation

Academic Article

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 (Ser1490). 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)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.
  • Published In

  • Science  Journal
  • Digital Object Identifier (doi)

    Author List

  • Pan W; Choi SC; Wang H; Qin Y; Volpicelli-Daley L; Swan L; Lucast L; Khoo C; Zhang X; Li L
  • Start Page

  • 1350
  • End Page

  • 1353
  • Volume

  • 321
  • Issue

  • 5894