Figure 10. Model for sequential activation of cortactin by deacetylation and phosphorylation.

Acetylated cortactin is inactive and probably has a closed conformation that masks the tyrosines targeted by Src. Upon appropriate stimulation, cortactin is deacetylated by HDAC6, exposing the tyrosines, which are then rapidly phosphorylated by Src. This phosphorylation keeps cortactin deacetylated. Whether this tyrosine-phosphorylated cortactin has an open or closed configuration is unknown (question mark).