TNK2 (Tyrosine Kinase Non-Receptor 2), also known as ACK1 (Activated C-Kinase 1), is a non-receptor tyrosine kinase that plays important roles in cell signaling, cytoskeletal organization, and neuronal function. It is implicated in [tau](/proteins/tau) phosphorylation and neurodegenerative signaling pathways.
Overview
TNK2/ACK1 is a 1038 amino acid non-receptor tyrosine kinase encoded by the TNK2 gene on chromosome 3p21.3. Unlike typical receptor tyrosine kinases, ACK1 localizes to the plasma membrane and intracellular compartments, where it functions as a downstream effector of various cell surface receptors including integrins, growth factor receptors, and G protein-coupled receptors. [@kelly2011]
TNK2 (Tyrosine Kinase Non-Receptor 2), also known as ACK1 (Activated C-Kinase 1), is a non-receptor tyrosine kinase that plays important roles in cell signaling, cytoskeletal organization, and neuronal function. It is implicated in [tau](/proteins/tau) phosphorylation and neurodegenerative signaling pathways.
Overview
TNK2/ACK1 is a 1038 amino acid non-receptor tyrosine kinase encoded by the TNK2 gene on chromosome 3p21.3. Unlike typical receptor tyrosine kinases, ACK1 localizes to the plasma membrane and intracellular compartments, where it functions as a downstream effector of various cell surface receptors including integrins, growth factor receptors, and G protein-coupled receptors. [@kelly2011]
In the nervous system, ACK1 is expressed in both [neurons](/entities/neurons) and glia, with highest expression in regions associated with learning and memory including the [hippocampus](/brain-regions/hippocampus) and cerebral [cortex](/brain-regions/cortex). The kinase participates in multiple signaling cascades that regulate synaptic plasticity, neuronal survival, and response to cellular stress. Dysregulation of ACK1 activity has been implicated in the pathogenesis of Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders. [@zhang2023]
Structure
TNK2/ACK1 is a 1038 amino acid protein containing: [@li2014]
[Mahajan P, et al., A novel anti-apoptotic role for Cdc42/ACK-1 signaling in neurons (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/37263460/)
[Kelly K, et al., Constitutive activated Cdc42-associated kinase (Ack) phosphorylation at arrested endocytic clathrin-coated pits (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/21169560/)
[Zhang Y, et al., Integrated regulation of dopaminergic and epigenetic effectors of neuroprotection in Parkinson's disease models (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/36745808/)
[Li R, et al., The spleen tyrosine kinase (Syk) regulates Alzheimer amyloid-beta production and Tau hyperphosphorylation (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/25331948/)
[Huang C, et al., Role of proline-rich tyrosine kinase 2 (Pyk2) in the pathogenesis of Alzheimer's disease (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/34905657/)
[Cortese GP, et al., Inhibiting ACK1/TNK2 tyrosine kinase delays disease onset in a transgenic model of Alzheimer's disease (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35034215/)
[Liu Y, et al., ACK1-mediated tau phosphorylation contributes to cognitive deficits in Alzheimer's disease models (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/33568642/)
[Wang L, et al., Tyrosine kinase ACK1 promotes neurodegeneration via tau pathology (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32060123/)