The p85 subunit of phosphoinositide 3-kinase is associated with beta-catenin in the cadherin-based adhesion complex.
Cell adhesion is fundamental to establishing and maintaining the discrete tissues in multicellular organisms. Adhesion must be sufficiently strong to preserve tissue architecture, whilst having the capacity to readily dissociate to permit fundamental processes, such as wound repair, to occur. However, very little is known about the signalling mechanisms involved in temporary down-regulation of cell adhesion to facilitate such processes. Cadherins are the principal mediators of cell-cell adhesion in a wide variety of tissues and species and form multi-protein complexes with cytosolic and cytoskeletal proteins to express their full adhesive capacity. In the present study we report that the p85 subunit of phosphoinositide 3-kinase (PI 3-kinase) is associated with the cadherin-based adhesion complex in human epithelial cells. The interaction of p85 with the complex is via beta-catenin. We also show that the interaction of p85 and beta-catenin is direct, involves the N-terminal Src homology domain 2 of p85 and is regulated by tyrosine phosphorylation. These data suggest that PI 3-kinase may play a role in the functional regulation of the cadherin-based adhesion complex.
Woodfield
R J
RJ
Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TA, U.K.
Hodgkin
M N
MN
Akhtar
N
N
Morse
M A
MA
Fuller
K J
KJ
Saqib
K
K
Thompson
N T
NT
Wakelam
M J
MJ
D000818:Animals; D015820:Cadherins / Q000302:isolation & purification / Q000378:metabolism*; D020134:Catalytic Domain; D002448:Cell Adhesion; D002460:Cell Line; D011232:Chemical Precipitation; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology / Q000378:metabolism; D046911:Macromolecular Substances; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators; D020798:Two-Hybrid System Techniques; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051176:beta Catenin; D004815:Epidermal Growth Factor; D005982:Glutathione Transferase; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors