Identification of a novel interaction between integrin β1 and 14-3-3β

Integrins are cell surface receptors for extracellular matrix, which play important roles ina a variety of biological processes. 14-3-3 proteins are a highly conserved family of cytoplasmic proteins that associate with several intracellular signaling molecules in regulation of various cellular functions. Here, we report identification of an interaction between the integrin beta1 cytoplasmic domain and 14-3-3 beta by using the yeast two-hybrid screen, Like several other proteins, the integrin beta1 cytoplasmic domain associated with 14-3-3 beta by a non-phosphoserine mechanism. The 14-3-3 beta /integrin beta1 interaction was confirmed by iir vitro binding assays as well as to-precipitation in vivo. Furthermore, we found that 14-3-3 beta co-localized with integrin beta1 during the early stage of cell spreading on fibronectin, suggesting a potential role of the 14-3-3 beta /integrin beta1 interaction in the regulation of cell adhesion. Using tetracycline-regulated expression system, we showed that overexpression of 14-3-3 beta stimulated cell spreading and migration on fibronectin but not on poly-L-lysine. However, the induced expression of 14-3-3 beta did not affect tyrosine phosphorylation of FAK or its substrates, p130(cas) and paxillin, suggesting that 14-3-3 beta regulated integrin-mediated cell spreading and migration by FAK-independent mechanisms. Taken together, these results identify an interaction between integrin and 14-3-3 proteins and suggest a potentially novel cellular function for 14-3-3 proteins in the regulation of integrin-mediated cell adhesion and signaling events.