DAP Kinase 1 (phospho Ser308) antibody [DKPS308]

Various apoptotic signals use Death Associated Protein Kinase (DAPK) as a downstream effector in different cell types. DAPK is a positive mediator of apoptosis and is widely expressed in many tissues of embryonic and adult origin. DAPK is a Ca2+/calmodulin dependent Ser/Thr kinase that associates with microfilaments. The protein is composed of a multidomain structure. It has a subdomain typical of serine/threonine kinases, a Ca²⁺/calmodulin regulatory domain, eight ankyrin repeats followed by two P-loop motifs and a typical death domain module. It contains two auto-inhibitory domains one of them Ca²⁺/calmodulin dependent. In the absence of this latter domain, DAPK is constitutively active. DAPK activity is also regulated by phosphorylation. DAPK was found to be negatively regulated by autophosphorylation at Ser308 which is in the calmodulin regulatory domain. This autophosphorylation, which occurs in cells at the basal state, lowers the affinity of DAPK for calmodulin and thus the kinase is inactive. Under some apoptotic conditions DAPK undergoes dephosphorylation. As a consequence, it binds to calmodulin with higher affinity, becomes activated, phosphorylates its downstream substrate proteins, and mediates apoptosis. Monoclonal antibodies specific for Phospho DAP-Kinase (pSer308) are important tools for studying the mechanism of DAPK activation in apoptosis.