Figure 2.

Schematic representation of signaling pathways and pathological processes regulated by PKD. The schematic representation shows the pathways that activate PKD and the various downstream signaling events and functions modulated by the kinase. PKD can be activated through stimulating various membrane receptors such as G-protein-coupled receptors (GPCRs) and growth factor receptors. The extracellular stimuli activate phospholipase C (PLC), which catalyzes the formation of diacylglycerol (DAG). DAG modulates PKD activation by binding and recruiting it to the cell membrane for activation by protein kinase C (PKC). PKD can also be activated on the outer mitochondrial membrane by oxidative stress through binding to DAG and PKC. Activated PKD is rapidly translocated from the plasma membrane to the cytosol and then to the nucleus, where it regulates a set of transcription factors in the nucleus. Activated PKD regulates a battery of pathological processes including cell proliferation, survival, migration, invasion, gene transcription, inflammation, angiogenesis, and secretion of tumor-associated factors through several major signaling pathways. Abbreviations: matrix metalloproteinase (MMP), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF), metastasis-associated 1 (MTA1), slingshot-1L (SSH1L), GPCR kinase-interacting protein 1 (GIT1).