Kinase Subfamily ASK

Kinase Classification: Group STE: Family STE11: Subfamily ASK

ASK is a stress responsive MAP3K that activates Jnk and p38 pathways in animals

Evolution

ASK is found throughout the holozoa. Mammals have three members, ASK1/MAP3K5, ASK2/MAP3K6, and ASK3/MAP3K7.

Domain Structure

ASK proteins have an N-terminal ASK_nt domain, followed by 3 TPR repeats, a kinase domain, an unannotated region, and a sam7 domain.

Biological Function

ASK (Apoptosis Specific Kinase) is activated by several stresses, including reactive oxygen, TNF signaling, LPS, and ER stress, and mediates both cell death as well as inflammatory responses [1]. ASK activates stress MAPK pathway, particularly through MKK4/MAPKK4 activation of p38 and JNK kinases [2]

References

1. Sakauchi C, Wakatsuki H, Ichijo H, and Hattori K. Pleiotropic properties of ASK1. Biochim Biophys Acta Gen Subj. 2017 Jan;1861(1 Pt A):3030-3038. DOI:10.1016/j.bbagen.2016.09.028 |
2. Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, Takagi M, Matsumoto K, Miyazono K, and Gotoh Y. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science. 1997 Jan 3;275(5296):90-4. DOI:10.1126/science.275.5296.90 |