Single Amino Acid Substitutions in Proteins of the armadillo Gene Family Abolish Their Binding to 
-Catenin (*)
- ¶ To whom correspondence should be addressed. Tel.: 49-761-5108471; Fax: 49-761-5108474; kemler{at}immunbio.mpg.de.mpg.de.
Abstract
Analysis of the calcium-dependent cell adhesion molecule E-cadherin has led to the identification of catenins, which are necessary
for cadherin function. Growing evidence that cadherins and catenins are subjected to genetic alterations in carcinogenesis
makes it especially important to understand protein-protein interactions within the cadherin-catenin complex. Here we report
the identification and analysis of the α-catenin binding site in plakoglobin (
-catenin). Using N- and C-terminal truncations of plakoglobin, we identified a domain of 29 amino acids necessary and sufficient
for binding α-catenin. The α-catenin binding site is fully encoded within exon 3 of plakoglobin but only partially represented
in Armadillo repeat 1. This suggests that exons rather than individual Arm repeats encode functional domains of plakoglobin.
Site-directed mutagenesis identified residues in the α-catenin binding site indispensable for binding in vitro. Analogous mutations in β-catenin and Armadillo had identical effects. Our results indicate that single amino acid mutations
in the α-catenin binding site of homologs of Armadillo could prevent a stable association with α-catenin, thus affecting cadherin-mediated
adhesion.
Footnotes
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↵§ Both authors contributed equally.
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- CCC
-
cadhedrin-catenin complex
- GST
-
glutathione S-transferase
- PCR
-
polymerase chain reaction
- PAGE
-
polyacrylamide gel electrophoresis.
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- Received July 27, 1995.
- Revision received November 10, 1995.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
