The Drosophila p21 activated kinase Mbt modulates DE-cadherin mediated cell adhesion by phosphorylation of Armadillo

Nicolas Menzel , Juliane Melzer , Jens Waschke , Christof E Lenz , Heike Wecklein , Guenter Lochnit , Detlev Drenckhahn , Thomas Raabe (1)

1 Institute of Medical Radiation and Cell Research

Phosphorylations by tyrosine and serine/threonine kinases regulate the interactions between components of the cadherin/catenin cell adhesion complex and thus can influence the dynamic modulation of cell adhesion under normal and disease conditions. Previous mutational analysis and localization experiments suggested an involvement of single members of the family of p21-activated kinases (PAKs) in the regulation of cadherin mediated cell adhesion, but the molecular mechanism remained elusive. We addressed this question using the Drosophila PAK protein Mbt, which is most similar to vertebrate PAK4. Previous phenotypic analysis showed that Mbt has a function to maintain adherens junctions during eye development and indicated a requirement of the protein in regulation of the actin cytoskeleton and the cadherin/catenin complex. Here we show that activation of Mbt leads to destabilization of the interaction of the Drosophila β-catenin homologue Armadillo with DE-cadherin resulting in a decrease in DE-cadherin mediated adhesion. Two conserved phosphorylation sites in Armadillo were identified that mediate this effect. Our findings support the previous observation that activation of the human Mbt homologue PAK4 leads to anchorage independent growth and provide a functional link between a PAK protein and the cadherin-catenin complex.

Mots clés: Life Sciences

Nicolas Menzel, Juliane Melzer, Jens Waschke, Christof E Lenz, Heike Wecklein, et al.. The Drosophila p21 activated kinase Mbt modulates DE-cadherin mediated cell adhesion by phosphorylation of Armadillo. Biochemical Journal, 2008, 416 (2), pp.231-241. ⟨10.1042/BJ20080465⟩. ⟨hal-00478988⟩