Cortactin (CTTN)

Cortactin is an actin-binding and cytoskeletal scaffold protein encoded by the CTTN gene located on chromosome 11q13[1][2][3]. It features modular domains: an N-terminal acidic region, a series of 6.5 highly conserved repeats, a proline-rich region, and a Src-homology 3 (SH3) domain, which mediate interactions with multiple proteins. Cortactin is a substrate for Src family tyrosine kinases and other kinases, undergoing extensive phosphorylation at multiple sites in response to extracellular signals[1][3]. The principal cellular role of cortactin is to regulate the polymerization and branching of actin filaments through activation and scaffolding of the Arp2/3 complex, promoting dynamic changes in cell shape, migration, and adhesion. These processes are critical for lamellipodia and invadopodia formation, cell migration, and invasion, making cortactin a central player in cancer metastasis and vascular barrier regulation[1][2]. Cortactin also influences endothelial barrier integrity and immune cell function, with dysfunction or overexpression implicated in acute lung injury, COPD, asthma, and multiple cancers. As a result, cortactin is monitored as a disease biomarker, though direct pharmacological targeting is limited due to its widespread cellular roles and potential safety concerns[1][2][3][4].

Other names

Src substrate cortactinEMS1AmplaxinOncogene EMS1Epididymis secretory sperm binding protein

Enhancement or inhibition of actin polymerization and cytoskeletal rearrangement via modulation of cortactin phosphorylation; Regulation of endothelial barrier function and cell migration by influencing signaling pathways (e.g., S1P and Rac signaling)