Not so simple: the complexity of phosphotyrosine signaling at cadherin adhesive contacts.

Cadherin cell-cell adhesion critically determines tissue organization and integrity in many organs of the body. Cadherin function influences patterning and morphogenesis while cadherin dysfunction contributes to disease, notably tumor invasion and metastasis. Cell signaling events are intimately linked with cadherin function; it is increasingly apparent that not only do cellular signals regulate cadherin function, but cadherins can also, in turn, modulate cell signaling itself. In this review, we discuss the complex interrelationship between phosphotyrosine-based cell signaling and cadherin adhesion. We focus on the interplay of events that occur at the cell surface and address three issues: the diverse mechanisms that activate phosphotyrosine signaling at cadherin cell-cell contacts, the functional impact of such signaling for cadherin adhesion, and the emerging capacity for cadherins to regulate growth factor signaling.