Expression of the receptor protein-tyrosine phosphatase, PTPmu, restores E-cadherin-dependent adhesion in human prostate carcinoma cells.
Normal prostate expresses the receptor protein-tyrosine phosphatase, PTPmu, whereas LNCaP prostate carcinoma cells do not. PTPmu has been shown previously to interact with the E-cadherin complex. LNCaP cells express normal levels of E-cadherin and catenins but do not mediate either PTPmu- or E-cadherin-dependent adhesion. Re-expression of PTPmu restored cell adhesion to PTPmu and to E-cadherin. A mutant form of PTPmu that is catalytically inactive was re-expressed, and it also restored adhesion to PTPmu and to E-cadherin. Expression of PTPmu-extra (which lacks most of the cytoplasmic domain) induced adhesion to PTPmu but not to E-cadherin, demonstrating a requirement for the presence of the intracellular domains of PTPmu to restore E-cadherin-mediated adhesion. We previously observed a direct interaction between the intracellular domain of PTPmu and RACK1, a receptor for activated protein kinase C (PKC). We demonstrate that RACK1 binds to both the catalytically active and inactive mutant form of PTPmu. In addition, we determined that RACK1 binds to the PKCdelta isoform in LNCaP cells. We tested whether PKC could be playing a role in the ability of PTPmu to restore E-cadherin-dependent adhesion. Activation of PKC reversed the adhesion of PTPmuWT-expressing cells to E-cadherin, whereas treatment of parental LNCaP cells with a PKCdelta-specific inhibitor induced adhesion to E-cadherin. Together, these studies suggest that PTPmu regulates the PKC pathway to restore E-cadherin-dependent adhesion via its interaction with RACK1.
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