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Title: The low-density lipoprotein receptor-related protein 10 is a negative regulator of the canonical Wnt/{beta}-catenin signaling pathway

Wnt signaling pathways play fundamental roles in the differentiation, proliferation and functions of many cells as well as developmental, growth, and homeostatic processes in animals. Low-density lipoprotein receptor (LDLR)-related protein (LRP) 5 and LRP6 serve as coreceptors of Wnt proteins together with Frizzled receptors, triggering activation of canonical Wnt/{beta}-catenin signaling. Here, we found that LRP10, a new member of the LDLR gene family, inhibits the canonical Wnt/{beta}-catenin signaling pathway. The {beta}-catenin/T cell factor (TCF) transcriptional activity in HEK293 cells was activated by transfection with Wnt3a or LRP6, which was then inhibited by co-transfection with LRP10. Deletion of the extracellular domain of LRP10 negated its inhibitory effect. The inhibitory effect of LRP10 was consistently conserved in HEK293 cells even when GSK3{beta} phosphorylation was inhibited by incubation with lithium chloride and co-transfection with constitutively active S33Y-mutated {beta}-catenin. Nuclear {beta}-catenin accumulation was unaffected by LRP10. The present studies suggest that LRP10 may interfere with the formation of the {beta}-catenin/TCF complex and/or its binding to target DNA in the nucleus, and that the extracellular domain of LRP10 is critical for inhibition of the canonical Wnt/{beta}-catenin signaling pathway.
Authors:
; ; ; ;  [1] ; ;  [2] ; ; ;  [1] ;  [1]
  1. Department of Molecular and Biochemical Nutrition, Graduate School of Human Life Science, Osaka City University, Osaka 558-8585 (Japan)
  2. Department of Animal Science, College of Agriculture and Life Science, Chonnam National University, Gwangju 500-757 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22202382
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 392; Journal Issue: 4; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; DNA; GENES; INCUBATION; INHIBITION; LIPOPROTEINS; LITHIUM CHLORIDES; PHOSPHORYLATION; RECEPTORS