DAPK1

Death-associated protein kinase 1 is a positive mediator of gamma-interferon induced programmed cell death. DAPK1 encodes a structurally unique 160-kD calmodulin dependent serine-threonine kinase that carries 8 ankyrin repeats and 2 putative P-loop consensus sites. It is a tumor suppressor candidate. [provided by RefSeq]

death-associated protein kinase 1

Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca2+ influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.

Isoform 2 cannot induce apoptosis but can induce membrane blebbing.

Apoptotic process Source: UniProtKB
Apoptotic signaling pathway Source: UniProtKB
Cellular response to hydroperoxide Source: ParkinsonsUK-UCL
Cellular response to interferon-gamma Source: UniProtKB
Defense response to tumor cell Source: ARUK-UCL
Intracellular signal transduction Source: UniProtKB
Negative regulation of translation Source: UniProtKB
Positive regulation of apoptotic process Source: GO_Central
Positive regulation of autophagy Source: ParkinsonsUK-UCL
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
Protein autophosphorylation Source: UniProtKB
Protein phosphorylation Source: UniProtKB
Regulation of apoptotic process Source: UniProtKB
Regulation of autophagy Source: UniProtKB
Regulation of NMDA receptor activity Source: UniProtKB

Cytoskeleton; Cytoplasm

Ubiquitinated by the BCR(KLHL20) E3 ubiquitin ligase complex, leading to its degradation by the proteasome.1 Publication
Removal of the C-terminal tail of isoform 2 (corresponding to amino acids 296-337 of isoform 2) by proteolytic cleavage stimulates maximally its membrane-blebbing function.
In response to mitogenic stimulation (PMA or EGF), phosphorylated at Ser-289; phosphorylation suppresses DAPK1 pro-apoptotic function. Autophosphorylation at Ser-308 inhibits its catalytic activity. Phosphorylation at Ser-734 by MAPK1 increases its catalytic activity and promotes cytoplasmic retention of MAPK1. Endoplasmic-stress can cause dephosphorylation at Ser-308.