<p>Cortactin was first identified as a tyrosine-phosphorylated protein in v-Src infected fibroblasts [<cite idref="PUB00034971"/>]. Cortactin has several domains: a N-terminal unstructured acidic domain, a central repeat domain, an alpha-helical domain, a proline rich domain, and finally, a highly conserved SH3 domain at the C terminus. The repeat domain is a series of six complete 37 amino acid tandemly repeating segments and one incomplete segment. The complete repeats, known as cortactin repeats, are predicted to form a helix-turn-helix structure [<cite idref="PUB00034972"/>].</p> <p>Cortactin appears to be phosphorylated by Src at several sites, and also binds directly to the SH2 domain of SRC. Phosphorylation by Src occurs downstream of a number of signalling pathways, including integrin-mediated adhesion and FGF stimulation [<cite idref="PUB00016991"/>]. The non-receptor kinases Fyn, Syk and Fer are also thought to play a role in cortactin tyrosine phosphorylation. Phosphorylation may cause a number of downstream events such as recruitment of other effector or regulatory proteins and conformational changes that affect cortactin activity.</p> <p>In addition to its roles in signal transduction, cortactin has been found to play a role in the actin cytoskeleton. The cortactin repeat region binds to filamentous actin with a K_d of 0.4 micromolar, and its N-terminal acidic domain binds to the Arp2/3 complex, which is a nucleator and cross linker of actin in vivo [<cite idref="PUB00034973"/>]. Cortactin may act to stabilise actin branches formed by the Arp2/3 complex.</p> <p>Cortactin's SH3 domain has been found to bind to numerous proteins including dynamin 2, N-WASP and WIP.</p> <p>Cortactin has been found in numerous organisms, including human, mouse and sea urchin.</p> Cortactin