Inositol pentakisphosphate mediates Wnt/beta-catenin signaling.

Inositol pentakisphosphate mediates Wnt/beta-catenin signaling. Research Abstract Details 

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Inositol pentakisphosphate mediates Wnt/beta-catenin signaling. Abstract Text:

Yuan Gao,Hsien-yu Wang,

Wnt3a stimulates lymphoid enhancer factor/T-cell factor protein-sensitive transcription, i.e. the canonical pathway, in mouse F9 embryonal tetratocarcinoma cells expressing rat Frizzled-1. We explored the potential roles for inositol polyphosphates as mediators of Wnt signaling in the canonical path-way. Wnt3a triggers G-protein-linked phosphatidylinositol signaling, transiently generating inositol polyphosphates, especially inositol pentakisphosphate (IP(5)) accumulation. Knock-down of Galpha(q) abolishes, whereas expression of the Q209L constitutively active mutant of Galpha(q) mimics, the effects of Wnt3a on IP(5) generation and downstream signaling. Phospholipase Cbeta-1 and Cbeta-3 mediate the G protein signal to the level of phosphatidylinositol signaling. Knock-down and inhibitor studies of the enzymes responsible for generating IP(5) reveal inositol 1,4,5-trisphosphate 3-kinase and inositol polyphosphate multikinase as key mediators in the production of IP(5). Wnt3a stimulation of the canonical pathway requires accumulation of IP(5), which acts to inhibit the activity of glycogen synthase kinase-3beta, whereas stimulating casein kinase 2. Blockade of Wnt3a stimulation of IP(5) generation blocks beta-catenin accumulation, activation of lymphoid enhancer factor/T-cell factor protein-sensitive transcription, and promotion of primitive endoderm formation in response to Wnt3a. Phosphatidylinositol signaling mediates Wnt3a action in the canonical pathway, acting to generate inositol pentakisphosphate, a key second messenger of Wnt3a.

Inositol pentakisphosphate mediates Wnt/beta-catenin signaling. Publishing Authors By Initials

Y Gao,HY Wang,

For similar proteins: armadillo domain proteins: beta catenin research abstracts see: proteins: armadillo domain proteins: beta catenin research

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Inositol pentakisphosphate mediates Wnt/beta-catenin signaling. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 26490-502

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 26

MONTH: 06

YEAR: 2007

Inositol pentakisphosphate mediates Wnt/beta-catenin signaling. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Inositol pentakisphosphate mediates Wnt/beta-catenin signaling. Keywords Mesh Terms:

KEYWORDS: beta Catenin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Inositol pentakisphosphate mediates Wnt/beta-catenin signaling. Information

Substance Name: GTP-Binding Protein alpha Subunits, Gq-G

Registry Number: EC 3.6.1.46

Grant and Affiliation Information for Inositol pentakisphosphate mediates Wnt/beta-catenin signaling.

AFFILIATION: Department of Physiology and Biophysics, Diabetes and Metabolic Disease Research Center, School of Medicine, Health Sciences Center, State University of New York, Stony Brook, New York 11794-8661, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM 069375

ACRONYM: GM

MEDLINETA: J Biol Chem

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