Domain Architecture of the Nonreceptor Tyrosine Kinase Ack1

The nonreceptor tyrosine kinase (NRTK) Ack1 comprises a distinct arrangement of non-catalytic modules. Its SH3 domain has a C-terminal to the kinase domain (SH1), in contrast to the typical SH3-SH2-SH1 layout in NRTKs. The Ack1 is the only protein that shares a region of high homology to the tumor suppressor protein Mig6, a modulator of EGFR. The vertebrate Acks make up the only tyrosine kinase (TK) family known to carry a UBA domain. The GTPase binding and SAM domains are also uncommon in the NRTKs. In addition to being a downstream effector of receptor tyrosine kinases (RTKs) and integrins, Ack1 can act as an epigenetic regulator, modulate the degradation of the epidermal growth factor receptor (EGFR), confer drug resistance, and mediate the progression of hormone-sensitive tumors. In this review, we discuss the domain architecture of Ack1 in relation to other protein kinases that possess such defined regulatory domains.

Automated summary

The nonreceptor tyrosine kinase Ack1 has a unique arrangement of non-catalytic modules, including an SH3 domain located at the C-terminal of the kinase domain (SH1), which differs from the typical layout in NRTKs. Ack1 shares a region of high homology with the tumor suppressor protein Mig6. It is the only tyrosine kinase family known to carry a UBA domain. The GTPase binding and SAM domains are also uncommon in the NRTKs. Ack1 acts as a downstream effector of receptor tyrosine kinases and integrins, as well as an epigenetic regulator and mediator of drug resistance and hormone-sensitive tumor progression.