Diacylglycerol kinase kappa (DGKK)

Diacylglycerol kinase kappa (DGKK) is a member of the diacylglycerol kinase family of enzymes, which catalyze the phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PA), thereby modulating the levels of these key lipid signaling molecules[1][2][5]. DGKK is classified as a type II diacylglycerol kinase and contains distinct structural domains such as an N-terminal pleckstrin homology domain, two cysteine-rich zinc finger-like (C1) domains, and a separated catalytic region[1][2]. It is a 1271-amino acid protein with a molecular mass of approximately 142 kDa[1][5]. DGKK displays tissue-specific expression, being most abundant in the testis and less so in the placenta[1]. Unlike other type II DGKs, DGKK localizes persistently to the plasma membrane and is uniquely regulated by tyrosine phosphorylation via the Src kinase pathway and by oxidative stress[1]. DGKK’s function is to regulate the balance between DAG and PA, both important second messengers in various signaling pathways, suggesting a critical role in cellular signal transduction and potentially in response to oxidative stress[1][2]. No DGKK-specific drugs or therapeutic antibodies are described in the current literature, nor are there established biomarkers or DGKK-specific clinical safety data. Most pharmacological research in the DGK family has centered on other isoforms such as DGKα and DGKζ[3]. DGKK is considered a valid molecular (enzyme) target due to its role in lipid signaling, though druggability and therapeutic relevance are largely unexplored[2][5].

Other names

Diacylglycerol kinase kappaDGKKDAG kinase kappaDGK-kappa142 kDa diacylglycerol kinaseDiglyceride kinase kappa

Not established for DGKK-specific drugs; for other DGKs, inhibition affects immune cell signaling pathways (e.g., T cell activation)