ASK-1

Apoptosis signal-regulating kinase 1, ASK-1, is part of the mitogen-activated protein kinase (MAPK) cascade. In humans it is also known as "mitogen-activated protein kinase kinase kinase 5", abbreviated as "MAP3K5".

Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. Phosphorylation of ASK-1 protein can lead to apoptosis or other cellular responses depending on the cell type. Northern blot analysis shows that ASK-1 transcript is abundantly expressed in human heart and pancreas. The ASK-1 (MAPKKK5) protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; ASK-1 does not activate MAPK/ERK.

ASK-1 found in the inactive form, bound to reduced thioredoxin. When oxidized by a reactive oxygen species, Trx dissociates from ASK-1. The ASK-1, which is found as a homo-oligodimer, autophosphorylates and becomes an active MAP kinase kinase kinase.

ASK-1 contains 1,374 amino acids with all 11 kinase subdomains. It is located on chromosome 6 at locus 6q22.33.