Death-associated protein kinase

Function

Death-associated protein kinase (DAPK) is a multi-domain serine/threonine kinase which regulates cell death mechanisms and has tumor suppression functions.^[1]

• DAPK1 is a positive mediator of γ-interferon induced programmed cell death.
  
• DAPK2 is a calcium/calmodulin dependent kinase involved in multiple cell signaling pathways which trigger cell survival.
  
• DAPK3 or zipper-interacting protein kinase is involved in the regulation of apoptosis.
  

Relevance

DAPK expression is lost in many types of cancer. DAPK1 expression is elevated in brains of Alzheimer Disease patients and in epilepsy patients. DAPK1 inhibitors are tested as drugs for attenuating acute brain injury.

Structural highlights

DAPK1 structure contains a small β sheet N-terminal lobe and a larger helix-rich C-terminal lobe. The ATP substrate is bound in a cleft between the two lobes. ^[2]