Dp71f Modulates GSK3- beta Recruitment to the beta 1-Integrin Adhesion Complex

Previously, it was shown that Dp71f binds to the beta 1-integrin adhesion complex to modulate PC12 cell adhesion. The absence of Dp71f led to a failure in the beta 1-integrin adhesion complex formation. One of the structural proteins which links the beta 1-integrin cytoplasmic domain to the actin cytoskeleton is ILK. GSK3- beta is an ILK substrate and the carboxi-terminal region of dystrophin 427 is a substrate for hierarchical phosphorylation by GSK3- beta . Dp71f contains the carboxi-terminal domain present in dystrophin 427. By using co-immunoprecipitation assays, in the present work it is demonstrated that in the neuronal PC12 cell line an interaction between Dp71f and GSK3- beta occurs. This interaction was corroborated by in vitro pulldown assays. We show that GSK3- beta is recruited to the beta 1-integrin complex and that a reduced expression of Dp71f induces a reduced GSK3- beta recruitment to the beta 1-integrin complex. In addition, the present work establishes that adhesion of PC12 cells to laminin does not influence the phosphorylation status of Dp71f.