Disease relevance of TAOK2

• In addition, immunoreactive MEK3 endogenous to Sf9 cells copurified with TAO1 produced from a recombinant baculovirus [1].
• A gene encoding PSKP-1 was synthesized and expressed in Escherichia coli [2].
• Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Study Group of Immunochemotherapy with PSK for Gastric Cancer [3].
• Combination of PSK with a low dose of docetaxel may be a new therapeutic strategy to treat patients with pancreatic cancer [4].
• Here, we show that cancer cells (PSK-1) derived from a patient with Klinefelter syndrome (47XXY) showing loss of an inactive X chromosome subsequently gained active X chromosomes [5].

High impact information on TAOK2

• We have assessed the efficacy of protein-bound polysaccharide (PSK) in addition to standard chemotherapy in patients who had undergone curative gastrectomy at 46 institutions in central Japan. 262 patients were randomly assigned standard treatment alone or with PSK [3].
• Addition of PSK to adjuvant chemotherapy with mitomycin and fluorouracil is beneficial as treatment after curative gastrectomy [3].
• Although PSK-alpha molecules have never been identified in any intact plant, reverse transcription-PCR analysis demonstrated that OsPSK is expressed in rice seedlings, indicating that PSK-alpha may be important for plant cell proliferation both in vitro and in vivo [6].
• Binding assays using 35S-labeled PSK-alpha demonstrated the existence of both high- and low-affinity specific saturable binding sites on the surface of rice cells in suspension [7].
• The pentapeptide [phytosulfokine-alpha (PSK-alpha)] very strongly stimulated colony formation of rice protoplasts at concentrations above 10(-8) M, indicating a similar mode of action in rice of phytosulfokines [7].

Chemical compound and disease context of TAOK2

• To investigate the effect of the BRMs on cellular growth and the characteristics of ER and progesterone receptors (PgR) in the human breast cancer cell line MCF-7, we used OK-432, Krestin (PSK), a protein-bound polysaccharide extracted from Coriolus versicolor, and lentinan, a fungal branched (1...3)-beta-D-glycan [8].
• Furthermore, in ER- breast cancer stage II patients, the effects of postoperative adjuvant therapy using MMC plus FT were compared with the effects of postoperative adjuvant therapy using MMC plus PSK [9].
• Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer [10].
• Between 1985 and 1988, the effect of using ftorafur (FT) or PSK (an immunotherapy agent) in combination with the conventional postoperative adjuvant therapy using mitomycin (MMC) plus tamoxifen (TAM) was assessed in stage II, oestrogen receptor-positive (ER+) breast cancer patients [9].
• For patients with advanced colorectal cancer, 5'-DFUR + PSK therapy may possibly be more useful than 5-FU + PSK, but further study is required [11].

Biological context of TAOK2

• Strains of C. elegans expressing active forms of TAO1 or KIN-18 exhibit altered pharyngeal electrophysiology as measured by electropharyngeogram [12].
• PSK encodes an open reading frame of 3705 nucleotides and contains an N-terminal kinase domain [13].
• In addition, PSKP-1 can be rendered active against trypsin by active-site site-specific mutagenesis, has bactericidal activity, and induces agglutination of red cells at micromolar concentrations [2].
• Our previous results shown that IL-2 and PSK regulate different nuclear transcription factors in NKL cells, and that the signal transduction pathway used by these inducers is different [14].
• Searching for bioactive peptides, we analyzed acidic extracts of Phyllomedusa sauvagii skin and found two new proteins, PSKP-1 and PSKP-2, of 6.7 and 6.6 kDa, respectively, which, by sequence homology, belong to the Kazal family of serine protease inhibitors [2].

Anatomical context of TAOK2

• The prostate-derived sterile 20-like kinase (PSK) regulates microtubule organization and stability [15].
• Some STE20s can also regulate the cytoskeleton, and we have shown that the germinal center kinase-like kinase prostate-derived STE20-like kinase (PSK) affects actin cytoskeletal organization [15].
• Kinase-defective PSK (K57A) was unable to reduce stress fibers [13].
• Stimulation of the NKL human NK cell line with interleukin-2 (IL-2) or protein-bound polysaccharide K (PSK) leads to sustained growth and cytolytic activity in comparison to unstimulated NKL cells [14].
• Recombinant PSKP-1 was purified from inclusion bodies, oxidatively refolded to the native state, and characterized by chemical, hydrodynamic and optical studies [2].

Associations of TAOK2 with chemical compounds

• Sorbitol, and to a lesser extent, sodium chloride, Taxol, and nocodazole increased TAO2 activity toward itself and kinase-dead MEKs 3 and 6 [16].
• To learn more about TAO/KIN-18 function, we studied how expression of constitutively active forms of TAO1 or KIN-18 would affect the physiology of intact worms [12].
• We found that TAO2 activity was increased by carbachol and that carbachol and the heterotrimeric G protein Galphao could activate p38 in 293 cells [17].
• PSKP-1 and PSKP-2 exhibit the unprecedented feature of having proline at P(1) and P(2) positions [2].
• The structure reveals that staurosporine occupies the position where the adenosine of ATP binds in TAO2, and the binding of the inhibitor mimics many features of ATP binding [18].

Physical interactions of TAOK2

• MEK3 coimmunoprecipitated with TAO1 when they were expressed in 293 cells [1].
• The association of PSK with microtubules results in the production of stabilized perinuclear microtubule cables that are nocodazole-resistant and contain increased levels of acetylated alpha-tubulin [15].

Regulatory relationships of TAOK2

• Cotransfection experiments suggested that TAO2 selectively activates MEK3 and MEK6 but not MEKs 1, 4, or 7 [16].

Other interactions of TAOK2

• The effects of PSK and IL-2 on these isoenzymes were different [14].
• PSKP-1 might protect P. sauvagii teguments from microbial invasion, by acting as an inhibitor of an as-yet unidentified prolyl endopeptidase or directly as a microbicidal compound [2].
• Conditioned medium (CM) was obtained from the following cell lines: MIA PaCa 2, PSK-1, PANC-1, and CAPAN-1 [19].

Analytical, diagnostic and therapeutic context of TAOK2

• Microinjection of PSK into cells results in localization of PSK to a vesicular compartment and causes a marked reduction in actin stress fibers [13].
• Oral administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in gut-associated lymphoid tissue (GALT) of specific-pathogen-free mice [20].
• The 5-year survival was 81.8% (95% CI 75.3-88.2%) in the PSK group and 72.1% (95% CI 61.4-82.7%) in the control group (P=0.056) [21].
• The 5-year disease-free survival was 73.0% (95% CI 65.6-80.4%) with PSK (n=137) and 58.8% (95% CI 47.1-70.5%) in the controls (n=68) (P=0.016) [21].
• To establish whether PSK has cytokine-inducing activities in vivo, we have orally administered PSK (1 g, the clinical dose) to 12 healthy volunteers and 9 gastric cancer patients who had undergone gastrectomy, and assessed the gene expression for cytokines in PBMC of each subject [22].

References