GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:15226396

From GONUTS
Jump to: navigation, search
Citation

Xu, G, Craig, AW, Greer, P, Miller, M, Anastasiadis, PZ, Lilien, J and Balsamo, J (2004) Continuous association of cadherin with beta-catenin requires the non-receptor tyrosine-kinase Fer. J. Cell. Sci. 117:3207-19

Abstract

The function of Type 1, classic cadherins depends on their association with the actin cytoskeleton, a connection mediated by alpha- and beta-catenin. The phosphorylation state of beta-catenin is crucial for its association with cadherin and thus the association of cadherin with the cytoskeleton. We now show that the phosphorylation of beta-catenin is regulated by the combined activities of the tyrosine kinase Fer and the tyrosine phosphatase PTP1B. Fer phosphorylates PTP1B at tyrosine 152, regulating its binding to cadherin and the continuous dephosphorylation of beta-catenin at tyrosine 654. Fer interacts with cadherin indirectly, through p120ctn. We have mapped the interaction domains of Fer and p120ctn and peptides corresponding to these sequences release Fer from p120ctn in vitro and in live cells, resulting in loss of cadherin-associated PTP1B, an increase in the pool of tyrosine phosphorylated beta-catenin and loss of cadherin adhesion function. The effect of the peptides is lost when a beta-catenin mutant with a substitution at tyrosine 654 is introduced into cells. Thus, Fer phosphorylates PTP1B at tyrosine 152 enabling it to bind to the cytoplasmic domain of cadherin, where it maintains beta-catenin in a dephosphorylated state. Cultured fibroblasts from mouse embryos targeted with a kinase-inactivating ferD743R mutation have lost cadherin-associated PTP1B and beta-catenin, as well as localization of cadherin and beta-catenin in areas of cell-cell contacts. Expression of wild-type Fer or culture in epidermal growth factor restores the cadherin complex and localization at cell-cell contacts.

Links

PubMed Online version:10.1242/jcs.01174

Keywords

Animals; Antennapedia Homeodomain Protein; Blotting, Western; Brain/embryology; Cadherins/metabolism; Catenins; Cell Adhesion; Cell Adhesion Molecules/metabolism; Cell Communication; Cell Membrane/metabolism; Cytoskeletal Proteins/metabolism; Cytoskeleton/metabolism; DNA, Complementary/metabolism; Dose-Response Relationship, Drug; Fibroblasts/metabolism; Glutathione Transferase/metabolism; Homeodomain Proteins/metabolism; Immunohistochemistry; Immunoprecipitation; Mice; Mutation; Neurons/metabolism; Nuclear Proteins/metabolism; Peptides/chemistry; Phenotype; Phosphoproteins/metabolism; Phosphorylation; Protein Binding; Protein Structure, Tertiary; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases/metabolism; Protein-Tyrosine Kinases; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins/physiology; Retina/embryology; Time Factors; Trans-Activators/metabolism; Transcription Factors/metabolism; Tyrosine/chemistry; Tyrosine/metabolism; beta Catenin

Significance

Annotations

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

CHICK:PTN1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P10288

F

Seeded From UniProt

complete

CHICK:O42486

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P10288

F

Seeded From UniProt

complete

CHICK:O42486

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P16591

F

Seeded From UniProt

complete

CHICK:CADH2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O13016

F

Seeded From UniProt

complete

CHICK:CADH2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O42486

F

Seeded From UniProt

complete

HUMAN:FER

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O42486

F

Seeded From UniProt

complete

Notes

See also

References

See Help:References for how to manage references in GONUTS.