Overexpression of PDZ-binding kinase confers malignant phenotype in prostate cancer via the regulation of E2F1.
A serine/threonine kinase PDZ binding-kinase (PBK) is a member of the mitogen-activated protein kinase (MAPK) kinase (MAPKK) family [1-3]. This enzyme is also known under the name T-lymphokine-activated killer cell-originated protein kinase (TOPK). PBK was discovered as a factor that binds PDZ2 domain of hDLg (human homologue of the Drosophila Discs-large (Dlg) tumor suppressor protein) . This study also demonstrated that the mitotic phosphorylation of PBK is required for its kinase activity . Due to this specific activation during the mitotic-phase of the cell cycle, PBK is also denoted as a “mitotic kinase”. PBK protein is phosphorylated by cdk1/ cyclin B during mitosis and its presence is necessary for formation of the mid-zone of the mitotic spindle . The PBK gene is especially highly expressed in placenta  and was also implicated in spermatogenesis [4,5]. Since PBK is expressed in seminiferous tubules of testis, where the male gametes are produced, it has been speculated that PBK might be essential in spermatocytogenesis during which mitosis occurs . While PBK is not expressed in the adult human brain  its mRNA is abundant in the human fetal brain  and rapidly dividing neuronal stem/progenitor cells (NS/PCs) . In mouse NS/PCs both Pbk and its downstream target p38 are essential for proliferation and self-renewal . In the adult mouse brain, Pbk is expressed in rapidly proliferating NS/PCs of the adult subventricular zone and early postnatal cerebellar external granular layer . The notion that PBK represents a stemnessassociated kinase is further supported by the evidence that PBK is down regulated during differentiation [6,7]. PBK is specifically expressed in all germinal zones during brain development and is not expressed in mature neurons and glial cells . A study conducted in HL-60 myeloid leukemia cells, induced to differentiate, using phorbol ester, showed that PBK protein expression was strongly down-regulated in differentiated cells . This study also showed that the expression of PBK correlated positively with the expression of a cell cycle regulator c-Myc.