Phosphorylation of beta-catenin and epidermal growth factor receptor by intestinal trefoil factor.
Intestinal trefoil factor (TFF3) is a member of the trefoil family of peptides, which are constitutively expressed in the gastrointestinal tract. TFF3 has been shown to promote migration of intestinal epithelial cells in vitro and to enhance epithelial restitution in vivo. In the present study, we show that the stimulatory effect of TFF3 on the migration of HT29 colonic carcinoma cells requires the perturbation of E-cadherin function, a calcium-dependent cell-cell adhesion molecule in epithelia. A rapid (< 1 minute) and specific tyrosine phosphorylation of beta-catenin and epidermal growth factor receptor was detected in cells treated with recombinant rat TFF3. No phosphorylation of E-cadherin or alpha-catenin was detected. Tyrosine phosphorylation of beta-catenin was associated with reduced membranous E-cadherin expression, perturbation of intercellular adhesion, and promotion of cell motility. These results suggest that TFF3 enhances cell migration through modulation of E-cadherin/catenin complex function. Tyrosine phosphorylation of beta-catenin and epidermal growth factor receptor seems to be involved in this process.
Liu
D
D
Division of Investigative Science, Imperial College of Science, Technology, and Medicine, Royal College of Surgeons, London, United Kingdom.
el-Hariry
I
I
Karayiannakis
A J
AJ
Wilding
J
J
Chinery
R
R
Kmiot
W
W
McCrea
P D
PD
Gullick
W J
WJ
Pignatelli
M
M
D000818:Animals; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D015534:Trans-Activators; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; C099037:TFF3 protein, rat; D015534:Trans-Activators; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D051176:beta Catenin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors