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PMID:7890674

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Citation

Rubinfeld, B, Souza, B, Albert, I, Munemitsu, S and Polakis, P (1995) The APC protein and E-cadherin form similar but independent complexes with alpha-catenin, beta-catenin, and plakoglobin. J. Biol. Chem. 270:5549-55

Abstract

The tumor suppressor APC protein associates with the cadherin-binding proteins alpha- and beta-catenin. To examine the relationship between cadherin, catenins, and APC, we have tested combinatorial protein-protein interactions in vivo, using a yeast two-hybrid system, and in vitro, using purified proteins. beta-Catenin directly binds to APC at high and low affinity sites. alpha-Catenin cannot directly bind APC but associates with it by binding to beta-catenin. Plakoglobin, also known as gamma-catenin, directly binds to both APC and alpha-catenin and also to the APC-beta-catenin complex, but not directly to beta-catenin. beta-Catenin binds to multiple independent regions of APC, some of which include a previously identified consensus motif and others which contain the centrally located 20 amino acid repeat sequences. The APC binding site on beta-catenin may be discontinuous since neither the carboxyl- nor amino-terminal halves of beta-catenin will independently associate with APC, although the amino-terminal half independently binds alpha-catenin. The catenins bind to APC and E-cadherin in a similar fashion, but APC and E-cadherin do not associate with each other either in the presence or absence of catenins. Thus, APC forms distinct heteromeric complexes containing combinations of alpha-catenin, beta-catenin, and plakoglobin which are independent from the cadherin-catenin complexes.

Links

PubMed

Keywords

Adenomatous Polyposis Coli Protein; Animals; Brain/metabolism; Cadherins/biosynthesis; Cadherins/isolation & purification; Cadherins/metabolism; Cell Adhesion Molecules/isolation & purification; Cell Adhesion Molecules/metabolism; Cloning, Molecular; Cytoskeletal Proteins/biosynthesis; Cytoskeletal Proteins/isolation & purification; Cytoskeletal Proteins/metabolism; Desmoplakins; Electrophoresis, Polyacrylamide Gel; Female; Gene Library; Genes, Tumor Suppressor; Humans; Immunoblotting; Kinetics; Pancreas/metabolism; Peptide Fragments/isolation & purification; Peptide Fragments/metabolism; Placenta/metabolism; Pregnancy; Recombinant Proteins/biosynthesis; Recombinant Proteins/isolation & purification; Recombinant Proteins/metabolism; Restriction Mapping; Saccharomyces cerevisiae/growth & development; Saccharomyces cerevisiae/metabolism; Trans-Activators; alpha Catenin; beta Catenin; gamma Catenin

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PLAK

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P25054

F

Seeded From UniProt

complete

HUMAN:CTNA1

enables

GO:0008013: beta-catenin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35222

F

Seeded From UniProt

complete

HUMAN:CTNA1

enables

GO:0045295: gamma-catenin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P14923

F

Seeded From UniProt

complete

HUMAN:CTNB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P25054

F

Seeded From UniProt

complete

HUMAN:CTNB1

enables

GO:0045294: alpha-catenin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35221

F

Seeded From UniProt

complete

HUMAN:APC

NOT|enables

GO:0045296: cadherin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:APC

enables

GO:0045295: gamma-catenin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P14923

F

Seeded From UniProt

complete

HUMAN:APC

enables

GO:0008013: beta-catenin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35222

F

Seeded From UniProt

complete

HUMAN:PLAK

enables

GO:0045294: alpha-catenin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35221

F

Seeded From UniProt

complete


See also

References

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