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p60v-src causes tyrosine phosphorylation and inactivation of the N-cadherin-catenin cell adhesion system
M Hamaguchi1, N Matsuyoshi, Y Ohnishi
1Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Japan.
Abstract:
Transformation of chick embryonic fibroblasts with Rous sarcoma virus strongly suppresses N-cadherin-mediated cell-cell adhesion, without inhibiting its expression. This suppression is correlated with tyrosine phosphorylation of N-cadherin and catenins, the cadherin-associated proteins, which are known to regulate cadherin function. Experiments with non-myristylation and temperature-sensitive mutants of RSV and with herbimycin A, a potent inhibitor of tyrosine kinases, suggest that both the suppression of cell adhesion and tyrosine phosphorylation of catenins are highly transformation-specific.
Insights
Rous sarcoma virus transformation suppresses N-cadherin cell adhesion by increasing tyrosine phosphorylation of N-cadherin and catenins. This suppression is specific to viral transformation and impacts cell-cell adhesion regulation.
Area of Science:
- Cell Biology
- Virology
- Biochemistry
Background:
- N-cadherin mediates cell-cell adhesion, crucial for tissue integrity.
- Rous sarcoma virus (RSV) transformation alters cell behavior.
- Cadherin-associated proteins (catenins) regulate cadherin function.
Purpose of the Study:
- To investigate the effect of RSV transformation on N-cadherin-mediated cell-cell adhesion.
- To determine the role of tyrosine phosphorylation in RSV-induced adhesion suppression.
Main Methods:
- Transformation of chick embryonic fibroblasts with Rous sarcoma virus.
- Analysis of N-cadherin expression and cell-cell adhesion.
- Assessment of tyrosine phosphorylation of N-cadherin and catenins.
- Use of RSV mutants and tyrosine kinase inhibitors (herbimycin A).
Main Results:
- RSV transformation strongly suppressed N-cadherin-mediated cell-cell adhesion without affecting N-cadherin expression.
- Suppression of adhesion correlated with increased tyrosine phosphorylation of N-cadherin and catenins.
- Adhesion suppression and catenin phosphorylation were transformation-specific.
Conclusions:
- RSV-induced suppression of cell-cell adhesion is mediated by tyrosine phosphorylation of N-cadherin and catenins.
- This mechanism is a specific consequence of viral transformation.