Mitogen-activated protein kinase kinase kinase 15 (MAP3K15)

Mitogen-activated protein kinase kinase kinase 15 (MAP3K15, also known as ASK3) is a member of the MAP kinase kinase kinase family of serine/threonine kinases. It acts as an upstream regulator in the stress-activated MAPK signaling cascade, leading to activation of downstream kinases such as p38 MAPK. MAP3K15 is involved in signal transduction in response to various cellular stresses, playing essential roles in apoptosis, cell death, and osmoregulation, particularly in the kidney where it participates in the WNK1-SPAK/OSR1 pathway linked to blood pressure control. Genetic studies have identified protein-truncating variants in MAP3K15 as protective against type 1 and type 2 diabetes, with expression also correlated with immune interactions and cancer prognosis (notably in osteosarcoma). Overall, MAP3K15 integrates cellular responses to stress, inflammation, and osmotic changes, and is considered a potential therapeutic target across diseases such as diabetes, hypertension, and cancer.

Other names

ASK3BA723P2.3M3K15_HUMAN

Upstream activation of p38 MAPK cascade; Phosphorylation and activation of MAP kinase kinases (MAP2Ks); Regulation of WNK1–SPAK/OSR1 pathway (blood pressure/osmotic stress)