Dynamic Interaction of PTPμ with Multiple Cadherins In Vivo

Abstract

There is a growing body of evidence to implicate reversible tyrosine phosphorylation as an important mechanism in the control of the adhesive function of cadherins. We previously demonstrated that the receptor protein tyrosine phosphatase PTPμ associates with the cadherin–catenin complex in various tissues and cells and, therefore, may be a component of such a regulatory mechanism (Brady-Kalnay, S.M., D.L. Rimm, and N.K. Tonks. 1995. J. Cell Biol. 130:977– 986). In this study, we present further characterization of this interaction using a variety of systems. We observed that PTPμ interacted with N-cadherin, E-cadherin, and cadherin-4 (also called R-cadherin) in extracts of rat lung. We observed a direct interaction between PTPμ and E-cadherin after coexpression in Sf9 cells. In WC5 cells, which express a temperature-sensitive mutant form of v-Src, the complex between PTPμ and E-cadherin was dynamic, and conditions that resulted in tyrosine phosphorylation of E-cadherin were associated with dissociation of PTPμ from the complex. Furthermore, we have demonstrated that the COOH-terminal 38 residues of the cytoplasmic segment of E-cadherin was required for association with PTPμ in WC5 cells. Zondag et al. (Zondag, G., W. Moolenaar, and M. Gebbink. 1996. J. Cell Biol. 134: 1513–1517) have asserted that the association we observed between PTPμ and the cadherin–catenin complex in immunoprecipitates of the phosphatase arises from nonspecific cross-reactivity between BK2, our antibody to PTPμ, and cadherins. In this study we have confirmed our initial observation and demonstrated the presence of cadherin in immunoprecipitates of PTPμ obtained with three antibodies that recognize distinct epitopes in the phosphatase. In addition, we have demonstrated directly that the anti-PTPμ antibody BK2 that we used initially did not cross-react with cadherin. Our data reinforce the observation of an interaction between PTPμ and E-cadherin in vitro and in vivo, further emphasizing the potential importance of reversible tyrosine phosphorylation in regulating cadherin function.

Toward a Functional Annotation of the Human Genome Using Artificial Transcription Factors

“…Shc is known to interact physically with PP2A (Ugi et al 2002) and cadherin (Xu et al 1997). Cadherins can also interact with a receptor-type protein tyrosine phosphatase (Brady-Kalnay et al 1998), in agreement with the presence of both cadherin and receptor-type protein tyrosine phosphatase in the IGF-2 group (Fig. 4).…”

Induction of phosphotyrosine in the gap junction protein, connexin431

“…The present results suggest that gap junctions in non-transformed cells might be targets for tyrosine kinases along with other types of cellular junctions and adhesion molecules [44][45][46][47]. The normal content of phosphotyrosine in Cx43 is clearly below the limit of detection.…”

Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells

“…This is even more intriguing since a molecular cross-talk between Wnt and EGF signalling is well known (Dierick and Bejsovec, 1999). Besides the kinases, several protein tyrosine phosphatases have been linked to b-catenin function (Hoschuetzky et al, 1994;Brady-Kalnay et al, 1995;Kypta et al, 1996). Future work will reveal which of the kinases or phosphatases is crucial for maintaining b-catenin in a dephosphorylated state in the case of sFRP-mediated signaling.…”