PKD3

Protein kinase D3 (PKD3, PRKD3) is a serine/threonine kinase of the protein kinase D family that functions downstream of diacylglycerol and protein kinase C signaling, integrating signals from growth factors, hormones, and G-protein-coupled receptor agonists to regulate cellular proliferation, survival, migration, and gene expression^[1][2]. Mechanistically, PKD3 participates in oncogenic signaling networks that control cell-cycle progression, metabolic reprogramming, and tumor-associated transcriptional responses, including activation of ERK1/c-MYC and NF-κB-associated pathways^[3][4][5]. In disease models, elevated PKD3 expression has been reported in prostate cancer, hepatocellular carcinoma, gastric cancer, and triple-negative breast cancer, where PKD3 promotes tumor growth, survival, invasion, and metastatic potential^[4][6][7]. PKD3 also contributes to glycolytic regulation through the p65/PFKFB3 axis, linking kinase signaling to cancer cell metabolic adaptation^[5]. Compared with related isoforms, PKD3 displays distinct biological properties, including constitutive localization in both the cytoplasm and nucleus and the absence of the C-terminal PDZ-binding motif present in PKD1 and PKD2, supporting isoform-specific signaling functions^[2]. Furthermore, PKD3 lacks the C-terminal autophosphorylation site found in other PKD family members, a feature associated with divergent regulatory behavior and downstream signaling outputs^[2]. For experimental applications, pharmacological PKD inhibitors such as CRT0066101 suppress PKD-dependent signaling, reduce proliferation and tumor growth in multiple cancer models, and are widely used to investigate PKD3-mediated mechanisms and therapeutic vulnerabilities^[8][9].