CAS/Crk signalling mediates uptake of Yersinia into human epithelial cells

Uptake of Yersinia pseudotuberculosis into mammalian cells involves engagem ent of beta1 integrin receptors by the bacterial protein invasin. This trig gers a host response that involves tyrosine phosphorylation of proteins and the induction of actin rearrangements that lead to cellular uptake of bact eria. In this report, we show that the focal adhesion protein CAS plays an important role in Yersinia uptake, and that its function is linked to the p hosphorylation-dependent interaction between CAS and Crk. These studies dem onstrate that Yersinia binding to host cell receptors initiates a cascade o f events involving tyrosine phosphorylation of GAS, subsequent formation of functional CAS-Crk complexes and the activity of the small GTP-binding pro tein Rac1. The delineation of this pathway lends support for a model in whi ch Yersinia uptake into human epithelial cells is dependent upon aspects of host signalling pathways that govern actin cytoskeleton remodelling and ce ll migration.