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NUAKs are AMPK-related kinases (ARKs). There are two known family members, NUAK1 (ARK5) and NUAK2 (SNARK), which are activated by liver kinase B1 (LKB1) and are important in cancer progression and metastasis, as well as carbohydrate metabolism.
|Cat No||Product Name / Activity|
|Potent and selective NUAK1 inhibitor|
|Potent and selective NUAK1/2 inhibitor|
NUAKs are AMPK-related kinases (ARK) and members of the calcium/calmodulin-dependent protein kinase-like (CAMKL) family of enzymes. Two NUAKs have been described, NUAK1 (ARK5) and NUAK2 (SNARK), both of which are 76kDa proteins containing an ubiquitin-associated domain located next to the C-terminal of the catalytic domain, which is required for liver kinase B1 (LKB1, also known as serine/threonine kinase 11) phosphorylation and activation. Myosin phosphatase complex subunit (MYPT1) is a substrate of both.
NUAK1 is expressed in heart, kidney, brain, liver and skeletal muscle, and is localized in the cytoplasm. Expression is associated with matrix metalloproteinases 2 and 9, and with the S100 calcium binding protein A4 (S100A4) and BRAF. NUAK1 promotes cancer cell survival and suppresses cell death during glucose starvation. It also has a role in facilitating cell motility and is a major factor in cancer cell migration and invasion. In addition, in tumor cells overexpressing MYC, NUAK1 is required for maintaining cell viability. It has been postulated that Akt mediates its effects on tumor cell survival and migration via NUAK1. Inhibition of NUAK1 has been shown to suppress tumor formation and prolong survival in a mouse model, suggesting the enzyme has potential as a target for cancer chemotherapy.
NUAK2 is expressed in kidney, thymus, spleen, stomach, and at high levels in skin, testis, uterus, ovary, adrenals and brain, and is primarily localized in the cell nucleus. NUAK2 expression is increased in the skeletal muscle of obese human subjects as well as in various cancers. Snark+/- knockout mice develop mature onset obesity and symptoms associated with type 2 diabetes mellitus in humans. Glucose deprivation increases both NUAK 1 and 2 activity. NUAK2 is also activated in response to other stresses, including hyperosmotic stress, DNA damage, oxidative stress and AMP, and like NUAK1, has a role in cancer cell motility and survival.
There are two currently recognized forms of programmed cell death: apoptosis and necroptosis. This poster summarizes the signaling pathways involved in apoptosis, necroptosis and cell survival following death receptor activation, and highlights the influence of the molecular switch, cFLIP, on cell fate.