Ack1

Activated Cdc42-associated kinase 1 (Ack1, E.C. 2.7.10.2), also known as TNK2, is a 114 kDa member of the Ack family of mammalian non-receptor tyrosine kinases (NRTKs) which is activated by multiple receptor tyrosine kinases (RTKs) to perform various roles within the cell.

Products
Background
Literature

Inhibitors

Cat No Product Name / Activity
4946 AIM 100
Potent and selective Ack1 (TNK2) inhibitor
5310 ASP 3026
Potent Ack (TNK2) inhibitor; also inhibits anaplastic lymphoma kinase (ALK)
5607 GNF 7
Ack1 and GCK inhibitor; inhibits Ras signaling
5098 KRCA 0008
Potent Ack1 and ALK dual inhibitor; orally bioavailable
6061 XMD 8-87
Potent Ack1/TNK2 inhibitor

Activated Cdc42-associated kinase 1 (Ack1, E.C. 2.7.10.2), also known as TNK2, is a 114 kDa member of the Ack family of mammalian non-receptor tyrosine kinases (NRTKs) which is activated by multiple receptor tyrosine kinases (RTKs) to perform various roles within the cell.

Ack1 is present in all cell types however it is more abundant in spleen, thymus and brain tissue. It was first identified as an inhibitor of the GTPase activity of GTP-bound Cdc42, but it also promotes cell survival via the phosphorylation of several effector proteins, such as the androgen receptor (AR) and protein kinase B (Akt). The kinase activity of Ack1 is regulated via the post-translational modification of several tyrosine residues. Ack1 is activated by growth factor binding and by homodimerization induced by cell adhesion.

In addition to a catalytic kinase domain, Ack1 contains seven other domains, which are important for substrate recognition, regulation of enzymatic activity, cellular localization and protein-protein interactions. Members of the Ack family are unique in that they are the only tyrosine kinases to have a CRIB domain, for interaction with Cdc42, and an SH3 domain C-terminal to the kinase domain. This complex domain structure results in a functionally diverse protein.

Mutations in the Ack1-encoding TNK2 gene have been linked to cancer, although overexpression and deregulation of Ack1 activation are more commonly associated with disease. Upregulation of Ack1 is associated with increased tumor invasion and recurrence of a number of different cancers, including hormone-refactory prostate cancer. In addition, its function as a regulator of transcription can promote growth of tamoxifen-resistant breast cancer. Ack1 has therefore become a target of cancer research which has shown that inhibitors of Ack1 can induce cancer cell apoptosis.

External sources of pharmacological information for Ack1 :

    Literature for Ack1

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