Abstract

The cdk5/p35 complex has been implicated in a variety of functions related to brain development, including axonal outgrown and neuronal migration. In this study, by co-immunoprecipitation and pull-down experiments, we have shown that the cdk5/p35 complex associates with and phosphorylates the neuronal δ-catenin. Immunocytochemical studies of δ-catenin and the cdk5-activator p35 in primary cortical neurons indicated that these proteins co-localize in the cell body of neuronal cells. In addition, cdk5 co-localized with β-catenin in the cell-cell contacts and plasma membrane of undifferentiated and differentiated N2A cells. In this context, we identified Ser 191 and Ser 246 on β-catenin structure as specific phosphorylation sites for cdk5/p35 complex. Moreover, Pin1, a peptidyl-prolyl isomerase (PPIase) directly bound to both, β- and δ-catenin, once they have been phosphorylated by the cdk5/p35 complex. Studies indicate that the cdk5/p35 protein kinase system is directly involved in the regulatory mechanisms of neuronal β- and δ-catenin. © 2006 Wiley-Liss, Inc.