Death-associated protein kinase 2 (DAPK2)

Death-associated protein kinase 2 (DAPK2) is a calcium/calmodulin-regulated serine/threonine protein kinase that plays crucial roles in regulating apoptosis (programmed cell death), autophagy, granulocyte differentiation, cell motility, and cytoskeletal dynamics[1][2][3][5]. It acts as a tumor suppressor by promoting apoptosis and autophagy, in part by phosphorylating key proteins such as SQSTM1/p62 and beclin-1, thereby affecting autophagy initiation and protein clearance[1][6]. DAPK2 is highly homologous to DAPK1 but is the smallest member of the DAPK family and lacks some protein-protein interaction domains found in DAPK1[2][4]. Its activity is tightly controlled by autoinhibition, phosphorylation, dimerization, and binding to other regulatory proteins such as calmodulin and 14-3-3[2][4]. DAPK2 expression is tissue-restricted and particularly strong in hematopoietic tissues, where it is required for neutrophil differentiation; decreased expression is associated with acute myeloid and promyelocytic leukemias[7]. While DAPK2 has been explored as a potential therapeutic target in cancer and inflammatory diseases, direct drugs are lacking; research tool compounds modulating its protein complexes have been described[2]. Dysregulation or loss of DAPK2 function contributes to leukemogenesis and possibly other malignancies, making its expression a potential biomarker for cancer prognosis and therapy monitoring[7][1].

Other names

Death-associated protein kinase 2DAPK2DAP kinase 2DAP-kinase-related protein 1DRP-1DRP1MGC119312

Inhibition or activation via modulation of kinase activity (e.g., by phosphorylation, autoinhibition, or protein-protein interactions) Potential modulation by small molecules that affect DAPK2:14-3-3 complex formation[2]