Biopolymers and cell. 2009; 25 (3): 169 - 180

Protein kinase ASK1 as potential therapeutic target

G. P. Volynets, V. G. Bdzhola, O. P. Kukharenko, O. V. Sovetova, S. M. Yarmoluk

Apoptosis signal-regulating kinase 1 (ASK1) is serine/threonine kinase of kinase 5 that activates MAP-kinase (MAPKKK5). ASK1 induces apoptosis via the JNK and p38 signaling pathways. This review is focused on three main characteristics of ASK1: the structure , the regulatory mechanisms of kinase activity and the physiological role. ASK1 is required for apoptosis induced by oxidative stress, TNF-a, Fas and endoplasmic reticulum. It also regulates differentiation and death of neurons. ASK1 has been shown to be required for the innate immune response. This kinase is a critical signaling molecule for cardiac hypertrophy and remodeling. ASK1 also accelerates endothelial cell senescence in diabetic patients. Inhibition of the ASK1-p38 pathway could be useful for preventing vascular ageing and treatment of neurodegenerative and cardiac diseases.

Keywords: ASK1, apoptosis, differentiation, immune response, cardiac hypertrophy.