Human Lymphokine-Activated Killer T-Cell-Originated Protein Kinase (PBK) Protein

Background

PDZ Binding Kinase (PBK), also known as TOPK (T-LAK cell-originated protein kinase), is a serine/threonine kinase that is predominantly expressed in proliferating cells and is associated with cell cycle regulation, particularly during the G2/M transition. It is highly active in mitosis, phosphorylating substrates such as histone H3 to regulate chromatin condensation and cell division. PBK is implicated in signaling pathways involving MAPKs and Akt, contributing to cell survival, proliferation, and response to stress stimuli. Overexpression of PBK has been observed in various cancers, including lung, breast, and colorectal cancers, where it promotes oncogenic traits like enhanced proliferation, invasion, and resistance to apoptosis. It has also been linked to the regulation of immune responses, influencing T-cell activation and cytokine production. PBK is tightly regulated through phosphorylation by upstream kinases, such as Cyclin-dependent kinases, and dephosphorylation by phosphatases like PP2A, which ensures its activity is restricted to specific phases of the cell cycle. Its potential as a therapeutic target is being explored due to its limited expression in normal tissues and overexpression in tumors, with inhibitors showing promise in preclinical studies by reducing cancer cell viability and enhancing sensitivity to chemotherapy.