Disease relevance of PBK

• These data show that PBK/TOPK protein is up-regulated in a variety of hematologic malignancies and may be involved in leukemic cell growth [1].
• To determine whether PBK/TOPK is upregulated in other mitotically active neoplastic cell lines and tissues, Northern analysis was performed on a panel of malignant cell lines and on clinical samples from patients with leukemia or lymphoma [2].
• PBK/TOPK is a novel mitotic kinase which is upregulated in Burkitt's lymphoma and other highly proliferative malignant cells [2].
• The study provides a molecular description of an ongoing fibrosis on the epithelial, stomal, and endothelial levels in PBK/ABK corneas [3].
• A total of 93 corneas were used for this study including 31 normal, 20 keratoconus, 19 bullous keratopathy (pseudophakic and aphakic, PBK/ABK), and 23 diabetic corneas [4].
• TOPK was shown to promote transformation in vitro and in vivo, and knockdown of TOPK in HCT116 colorectal cancer cells reduced this cell lines' tumorigenic properties in vitro and in vivo [5].

Psychiatry related information on PBK

• RESULTS: The speech perception performance of the 15 children with AN able to complete a PBK-word assessment, fell into two distinct categories [6].
• Ten SPK recipients died during the study time period [7].

High impact information on PBK

• We propose that ATR and ATM regulate SPK activity through a feedback mechanism originating at active replicons [8].
• Analysis of in vitro phosphorylation indicated that SPK phosphorylated specifically a Ser residue in Suc synthase that has been shown to be important for its activity in the degradation of Suc [9].
• This evidence shows how PBK could link hDlg or other PDZ-containing proteins to signal transduction pathways regulating the cell cycle or cellular proliferation [10].
• Immunocytochemical analysis with anti-PBK/TOPK antibody implicated a critical role of PBK/TOPK in an early step of mitosis [11].
• Reduction of PBK/TOPK expression by small interfering RNA resulted in significant suppression of cell growth probably due to dysfunction in the cytokinetic process [11].

Chemical compound and disease context of PBK

• RESULTS: Melanoma cell lines expressing high levels of TOPK were more resistant to arsenite (As(3+))-induced apoptosis [12].

Biological context of PBK

• PBK and hDlg are phosphorylated at mitosis in HeLa cells, and the mitotic phosphorylation of PBK is required for its kinase activity [10].
• Previous work has shown up-regulated expression of PBK/TOPK mRNA in a variety of tumor cell lines and fetal tissues, suggesting a role for this kinase in malignant cell proliferation [1].
• We performed genomic subtraction coupled to microarray-based gene expression profiling and identified the PDZ (postsynaptic density-95/Discs large/zona occludens-1)-binding kinase/T-LAK (lymphokine-activated killer T cell) cell originating protein kinase (PBK/TOPK) as a gene highly enriched in neural stem cell cultures [13].
• The open reading frame of the TOPK gene encodes a protein of 322 amino acids, possessing a protein kinase domain profile [14].
• Tissue distribution of TOPK mRNA expression was specific for the testis, T-LAK cells, activated lymphoid cells, and lymphoid tumors [14].

Anatomical context of PBK

• Furthermore, ablation of the adult stem cell population leads to concomitant loss of PBK/TOPK-positive cells in the SEZ [13].
• Cloning and expression of a novel MAPKK-like protein kinase, lymphokine-activated killer T-cell-originated protein kinase, specifically expressed in the testis and activated lymphoid cells [14].
• SPK mRNA was localized to the outer cell layer of seminiferous tubules by in situ hybridization, suggesting involvement of it in the process of spermatogenesis [15].
• In interphase cells, TOPK expresses in cytosol and nucleus without any significant association with microtubule networks [16].
• PBK/ABK and Fuchs' dystrophy corneas had decreased endothelial cell staining compared with normal [17].

Associations of PBK with chemical compounds

• PBK/TOPK is a recently cloned serine/threonine kinase which is phosphorylated during mitosis [2].
• PBK/TOPK is a recently identified 322 amino acid serine/threonine kinase that is phosphorylated during mitosis and may include p38 MAPK among its targets [1].
• In the present study, we demonstrate that PBK is down regulated during doxorubicin induced growth arrest of HL60 promyelocytic leukemia cells at least partly due to cell cycle-specific transcriptional regulation [18].
• PBK modeling for metals. Examples with lead, uranium, and chromium [19].
• Treatment with the phosphatidylinositol 3'-kinase (PBK) inhibitor LY294002 resulted in ICAM-5 down-regulation [20].

Physical interactions of PBK

• In vitro, PBK binds specifically to PDZ2 of hDlg through its C-terminal T/SXV motif [10].

Regulatory relationships of PBK

• PBK/TOPK and activated serin kinase 2 (PAK2) are novel serin kinases that have recently been identified [21].

Other interactions of PBK

• We investigated the intracellular distribution of TOPK and its association with cdk1/cyclin B and microtubules [16].
• Furthermore, when HL-60 myeloid leukemic cells were differentiated with phorbol ester (TPA), PBK/TOPK protein expression was strongly down-regulated by 24 h [1].
• Therefore, accumulation of TN-C in PBK/ABK corneas was accompanied by an increased expression of its three binding integrins, especially alphaVbeta6 in the corneal epithelium [22].
• IGF-I and BMP-4 RNA levels were increased in PBK/ABK [4].
• BMP-2 gene expression was lower than normal in the PBK/ABK and diabetic corneas [4].

Analytical, diagnostic and therapeutic context of PBK

• Northern blot analysis indicated that SPK mRNA was predominantly expressed in testis [15].
• SPK gene was assigned to human chromosome 8p21.2 by radiation hybrid [15].
• Indirect immunofluorescence with antibodies to 27 ECM components was used on frozen sections of 14 normal and 20 PBK/ABK corneas [3].
• The most common primary indications for corneal transplantation were vascularized corneal scar in 31 of the 86 eyes (36%), followed by pseudophakic and aphakic bullous keratopathy (PBK, ABK) [23].
• RT-PCR analysis also showed elevated levels of beta6 mRNA in PBK/ABK compared to normal corneas [22].

References