DAPK1 Protein, Human (Active, sf9, His-GST)

DAPK1 protein, a calcium/calmodulin-dependent serine/threonine kinase, intricately participates in multiple cellular signaling pathways, regulating cell survival, apoptosis, and autophagy. Its versatile role includes orchestrating both type I apoptotic and type II autophagic cell death signals, the former being caspase-dependent and the latter characterized by the accumulation of autophagic vesicles and being caspase-independent. DAPK1 engages in phosphorylation events with diverse substrates: it inhibits the catalytic activity, nuclear localization, and cellular function of PIN1, enhances stress fiber formation in endothelial cells by phosphorylating TPM1, and significantly decreases the binding of STX1A to STXBP1. Additionally, it phosphorylates PRKD1 to regulate JNK signaling under oxidative stress and modulates autophagy by phosphorylating BECN1, disrupting its interaction with BCL2 and BCL2L1. DAPK1 also phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. In the context of extrasynaptic NMDA receptors, DAPK1 acts as a signaling amplifier, mediating brain damage in stroke by inducing injurious Ca(2+) influx through NMDA receptor channels. Furthermore, DAPK1 collaborates with DAPK3 to phosphorylate RPL13A upon interferon-gamma activation, leading to transcript-selective translation inhibition. Notably, isoform 2 of DAPK1 lacks the ability to induce apoptosis but retains the capacity to induce membrane blebbing.