Activated CDC42 kinase 1 (ACK1)

Activated CDC42 kinase 1 (ACK1; encoded by TNK2) is a multi-domain, non-receptor tyrosine kinase that functions as a cytosolic effector for the small GTPase CDC42[5][6]. It is activated downstream of several receptor tyrosine kinases, most notably the epidermal growth factor receptor (EGFR), and plays a key role in signal transduction to promote cell proliferation, survival, migration, and regulation of endocytosis[1][2][3]. ACK1 possesses unique structural features, including a sterile alpha motif (SAM), tyrosine kinase domain, SH3 domain, CRIB motif for binding to CDC42, a clathrin binding region, an EGFR-binding domain, and a carboxy-terminal ubiquitin association (UBA) domain, which mediates interactions with ubiquitinated proteins and EGFR turnover[5]. Dysregulation of ACK1 activity—via overexpression or activating mutations—is associated with cancer onset and progression, and experimental inhibition of ACK1 suppresses cancer cell growth in vitro and in vivo, making ACK1 a potential therapeutic target in oncology. No clinically approved drugs specifically target ACK1, but its documented roles in various cancers have prompted ongoing research to develop selective inhibitors[3][5].

Other names

TNK2ACKCdc42-associated tyrosine kinase 1Activated CDC42-associated kinase 1

Inhibition of ACK1 kinase activity, leading to reduced proliferation, survival, migration, and radioresistance of cancer cells[3]. Suppression of downstream signaling from receptor tyrosine kinases (e.g., EGFR)[1][3].