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Title: A conserved phosphorylation switch controls the interaction between cadherin and β-catenin in vitro and in vivo

In metazoan adherens junctions, β-catenin links the cytoplasmic tail of classical cadherins to the F-actin-binding protein α-catenin. Phosphorylation of a Ser/Thr-rich region in the cadherin tail dramatically enhances affinity for β-catenin and promotes cell-cell adhesion in cell culture systems, but its importance has not been demonstrated in vivo. In this paper, we identify a critical phosphorylated serine in the C. elegans cadherin HMR-1 required for strong binding to the β-catenin homolog HMP-2. Ablation of this phosphoserine interaction produces developmental defects that resemble full loss-of-function (Hammerhead and Humpback) phenotypes. Most metazoans possess a single gene for β-catenin, which is also a transcriptional coactivator in Wnt signaling. Nematodes and planaria, however, have a set of paralogous β-catenins; for example, C. elegans HMP-2 functions only in cell-cell adhesion, whereas SYS-1 mediates transcriptional activation through interactions with POP-1/Tcf. Finally, our structural data define critical sequence differences responsible for the unique ligand specificities of these two proteins.
Authors:
 [1] ;  [2] ;  [2] ;  [1] ;  [2] ;  [3]
  1. Seoul National Univ., Seoul (South Korea)
  2. Univ. of Wisconsin, Madison, WI (United States)
  3. Stanford Univ. School of Medicine, Stanford, CA (United States)
Publication Date:
Grant/Contract Number:
2013R1A1A2061541; R21 HD072769; R01 GM58038; R01 GM56169; U01 GM09463
Type:
Published Article
Journal Name:
Developmental Cell
Additional Journal Information:
Journal Volume: 33; Journal Issue: 1; Journal ID: ISSN 1534-5807
Publisher:
Cell Press - Elsevier
Research Org:
Stanford Univ., CA (United States); Seoul National Univ. (Korea, Republic of)
Sponsoring Org:
USDOE; National Inst. of Health (NIH) (United States); National Research Foundation of Korea (NRF)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1250099
Alternate Identifier(s):
OSTI ID: 1347142