The regulation of cadherin-mediated adhesion by tyrosine phosphorylation/dephosphorylation of beta-catenin.
The formation of stable cell-cell adhesions by type I cadherins depends on the association of their cytoplasmic domain with beta-catenin, and of beta-catenin with alpha-catenin. The binding of beta-catenin to these partners is regulated by phosphorylation of at least three critical tyrosine residues. Each of these residues is targeted by one or more specific kinases: Y142 by Fyn, Fer and cMet; Y489 by Abl; and Y654 by Src and the epidermal growth factor receptor. Developmental and physiological signals have been identified that initiate the specific phosphorylation and dephosphorylation of these residues, regulating cadherin function during neurite outgrowth, permeability of airway epithelium and synapse remodeling, and possibly initiating epithelial cell migration during development and metastasis.
Lilien
Jack
J
Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242, USA. jack-lilien@uiowa.edu
Balsamo
Janne
J
D000818:Animals; D015820:Cadherins / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D008958:Models, Molecular; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism* / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism*
D015820:Cadherins; D014157:Transcription Factors; D051176:beta Catenin; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases