title: A conserved phosphorylation switch controls the interaction between cadherin and β-catenin in vitro and in vivo.
abstract: 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. Here, 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. Our structural data define critical sequence differences responsible for the unique ligand specificities of these two proteins.
authors: School of Biological Sciences, Seoul National University, Seoul 151-747, South Korea. Electronic address: choihj@snu.ac.kr.
authors: Hee-Jung
authors: HJ
authors: Choi
authors: Program in Cellular and Molecular Biology, University of Wisconsin, Madison, WI 53706, USA.
authors: Timothy
authors: T
authors: Loveless
authors: Department of Zoology, University of Wisconsin, Madison, WI 53706, USA.
authors: Allison M
authors: AM
authors: Lynch
authors: School of Biological Sciences, Seoul National University, Seoul 151-747, South Korea.
authors: Injin
authors: I
authors: Bang
authors: Program in Cellular and Molecular Biology, University of Wisconsin, Madison, WI 53706, USA; Department of Zoology, University of Wisconsin, Madison, WI 53706, USA.
authors: Jeff
authors: J
authors: Hardin
authors: Departments of Structural Biology and of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: bill.weis@stanford.edu.
authors: William I
authors: WI
authors: Weis
mesh_terms: D022005:Adherens Junctions / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C502083:Sys-1 protein, C elegans; D014157:Transcription Factors; D051176:beta Catenin; C450060:hmr-1 protein, C elegans; C096787:pop-1 protein, C elegans; D012694:Serine