The signal transduction from extracellular ligands to the actin cytoskeleton involves tyrosine phosphorylation of a filamentous actin associated protein, cortacin. Cortacin has a unique protein structure consisting of multiple copies of a repeat unit of 37 aminoacids and a SH3 domain at the COOH-terminus. In vitro, cortacin forms a dimmer and cross-links efficiently filamentous actin. Tyrosine phosphorylation mediated by protein tyrosine kinase Src disrupts the dimerization of cortacin and results in a decrease in its activity for F-actin cross-linking. Within adherent cells, cortacin is associated with cell peripheral areas such as lamellipodia and membrane ruffles. Overexpression of wild-type cortacin can potentiate the cellular motility, whereas mutations at tyrosine phosphorylation impair cell migration. In addition to transient association with Src protein tyrosine kinases, cortacin binds to multiple intracellular proteins via its SH3 domain. These proteins include ZO1, CBP90, and CortBP1. Interestingly, these proteins are often involved in cell-cell communications. Thus, cortacin may play an important role in transducing extracellular signals for cell migration, shape change, cell contact and cell development by virtue of its ability to modulate directly the function of the actin cytoskeleton.