Protein kinase D (PKD)

Protein kinase D (PKD) denotes a family of serine/threonine kinases—PKD1, PKD2, and PKD3—involved in the regulation of a wide array of cellular processes, including proliferation, survival, differentiation, migration, secretion, immune signaling, and more[1][5]. PKD enzymes act downstream of diacylglycerol (DAG) and protein kinase C (PKC) and are members of the calcium/calmodulin-dependent kinase (CaMK) superfamily[1][3][4]. Dysregulation of PKD expression or activity has been implicated in many diseases, particularly cancer, inflammation, cardiac disorders, and metabolic diseases. PKD family members have distinct as well as overlapping roles; for example, PKD1 acts as a tumor suppressor in some cancers, while PKD2 and PKD3 often drive cell proliferation and resistance to therapy[6][5]. Several small-molecule inhibitors targeting PKD have been developed and evaluated in preclinical studies, some showing suppression of tumor growth and metastasis in animal models, though clinical translation is limited by specificity, delivery, and isoform-selectivity issues[4][6]. PKD isoform expression profiling and pathway analyses are emerging as potential biomarkers for therapeutic targeting and patient stratification in oncology and other disease settings[6][4][1].

Other names

PKDPKD1PKD2PKD3PKCμ (for PKD1)PKCν (for PKD3)Protein kinase D familySerine/threonine-protein kinase D

Inhibition of PKD kinase activity (small molecule inhibitors reduce cell proliferation, induce apoptosis, inhibit survival and metastasis)[4][6]. Modulation of downstream survival and proliferation pathways (e.g., inhibition of NF-κB activation, Hsp27 phosphorylation)[4]. Isoform-dependent modulation (inhibiting pro-oncogenic PKD2/PKD3 or restoring tumor-suppressive PKD1)[6].