cdk5 modulates beta- and delta-catenin/Pin1 interactions in neuronal cells.
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 delta-catenin. Immunocytochemical studies of delta-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 beta-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 beta-catenin structure as specific phosphorylation sites for cdk5/p35 complex. Moreover, Pin1, a peptidyl-prolyl isomerase (PPIase) directly bound to both, beta- and delta-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 beta- and delta-catenin.
Muñoz
Juan P
JP
Laboratory of Cellular, Molecular Biology and Neurosciences, Faculty of Sciences, Millennium Institute for Advanced Studies in Cell Biology and Biotechnology, Department of Neurological Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Huichalaf
Claudia H
CH
Orellana
Daniel
D
Maccioni
Ricardo B
RB
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D051360:Cyclin-Dependent Kinase 5 / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D051185:gamma Catenin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C414604:PDZD2 protein, rat; D051176:beta Catenin; D051185:gamma Catenin; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat