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Gene Review

TAOK2  -  TAO kinase 2

Homo sapiens

Synonyms: KIAA0881, Kinase from chicken homolog C, MAP3K17, PSK, PSK-1, ...
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Disease relevance of TAOK2


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


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


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


  1. Isolation of TAO1, a protein kinase that activates MEKs in stress-activated protein kinase cascades. Hutchison, M., Berman, K.S., Cobb, M.H. J. Biol. Chem. (1998) [Pubmed]
  2. A Kazal prolyl endopeptidase inhibitor isolated from the skin of Phyllomedusa sauvagii. Gebhard, L.G., Carrizo, F.U., Stern, A.L., Burgardt, N.I., Faivovich, J., Lavilla, E., Ermácora, M.R. Eur. J. Biochem. (2004) [Pubmed]
  3. Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Study Group of Immunochemotherapy with PSK for Gastric Cancer. Nakazato, H., Koike, A., Saji, S., Ogawa, N., Sakamoto, J. Lancet (1994) [Pubmed]
  4. PSK-mediated NF-kappaB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1. Zhang, H., Morisaki, T., Nakahara, C., Matsunaga, H., Sato, N., Nagumo, F., Tadano, J., Katano, M. Oncogene (2003) [Pubmed]
  5. Characterization of loss-of-inactive X in Klinefelter syndrome and female-derived cancer cells. Kawakami, T., Zhang, C., Taniguchi, T., Kim, C.J., Okada, Y., Sugihara, H., Hattori, T., Reeve, A.E., Ogawa, O., Okamoto, K. Oncogene (2004) [Pubmed]
  6. Oryza sativa PSK gene encodes a precursor of phytosulfokine-alpha, a sulfated peptide growth factor found in plants. Yang, H., Matsubayashi, Y., Nakamura, K., Sakagami, Y. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  7. Phytosulfokine-alpha, a sulfated pentapeptide, stimulates the proliferation of rice cells by means of specific high- and low-affinity binding sites. Matsubayashi, Y., Takagi, L., Sakagami, Y. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  8. Effects of OK-432 (picibanil) on the estrogen receptors of MCF-7 cells and potentiation of antiproliferative effects of tamoxifen in combination with OK-432. Aoyagi, H., Iino, Y., Takeo, T., Horii, Y., Morishita, Y., Horiuchi, R. Oncology (1997) [Pubmed]
  9. Postoperative adjuvant randomised trial comparing chemoendocrine therapy, chemotherapy and immunotherapy for patients with stage II breast cancer: 5-year results from the Nishinihon Cooperative Study Group of Adjuvant Chemoendocrine Therapy for Breast Cancer (ACETBC) of Japan. Morimoto, T., Ogawa, M., Orita, K., Sugimachi, K., Toge, T., Dohi, K., Nomura, Y., Monden, Y., Ogawa, N. Eur. J. Cancer (1996) [Pubmed]
  10. Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer. Alliot, C. Br. J. Cancer (2004) [Pubmed]
  11. A randomized controlled trial of postoperative adjuvant immunochemotherapy for colorectal cancer with oral medicines. Koda, K., Miyazaki, M., Sarashina, H., Suwa, T., Saito, N., Suzuki, M., Ogawa, K., Watanabe, S., Kodaira, S., Nakazato, H. Int. J. Oncol. (2003) [Pubmed]
  12. kin-18, a C. elegans protein kinase involved in feeding. Berman, K.S., Hutchison, M., Avery, L., Cobb, M.H. Gene (2001) [Pubmed]
  13. PSK, a novel STE20-like kinase derived from prostatic carcinoma that activates the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and regulates actin cytoskeletal organization. Moore, T.M., Garg, R., Johnson, C., Coptcoat, M.J., Ridley, A.J., Morris, J.D. J. Biol. Chem. (2000) [Pubmed]
  14. Different regulation of PKC isoenzymes and MAPK by PSK and IL-2 in the proliferative and cytotoxic activities of the NKL human natural killer cell line. García-Lora, A., Martinez, M., Pedrinaci, S., Garrido, F. Cancer Immunol. Immunother. (2003) [Pubmed]
  15. The prostate-derived sterile 20-like kinase (PSK) regulates microtubule organization and stability. Mitsopoulos, C., Zihni, C., Garg, R., Ridley, A.J., Morris, J.D. J. Biol. Chem. (2003) [Pubmed]
  16. Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2. Chen, Z., Cobb, M.H. J. Biol. Chem. (2001) [Pubmed]
  17. TAO (thousand-and-one amino acid) protein kinases mediate signaling from carbachol to p38 mitogen-activated protein kinase and ternary complex factors. Chen, Z., Raman, M., Chen, L., Lee, S.F., Gilman, A.G., Cobb, M.H. J. Biol. Chem. (2003) [Pubmed]
  18. Crystal structure of the MAP3K TAO2 kinase domain bound by an inhibitor staurosporine. Zhou, T.J., Sun, L.G., Gao, Y., Goldsmith, E.J. Acta Biochim. Biophys. Sin. (Shanghai) (2006) [Pubmed]
  19. Putative pancreatic cancer-associated diabetogenic factor: 2030 MW peptide. Basso, D., Valerio, A., Seraglia, R., Mazza, S., Piva, M.G., Greco, E., Fogar, P., Gallo, N., Pedrazzoli, S., Tiengo, A., Plebani, M. Pancreas (2002) [Pubmed]
  20. 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. Harada, M., Matsunaga, K., Oguchi, Y., Iijima, H., Tamada, K., Abe, K., Takenoyama, M., Ito, O., Kimura, G., Nomoto, K. Int. J. Cancer (1997) [Pubmed]
  21. Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study. Ohwada, S., Ikeya, T., Yokomori, T., Kusaba, T., Roppongi, T., Takahashi, T., Nakamura, S., Kakinuma, S., Iwazaki, S., Ishikawa, H., Kawate, S., Nakajima, T., Morishita, Y. Br. J. Cancer (2004) [Pubmed]
  22. Induction of gene expression for immunomodulating cytokines in peripheral blood mononuclear cells in response to orally administered PSK, an immunomodulating protein-bound polysaccharide. Kato, M., Hirose, K., Hakozaki, M., Ohno, M., Saito, Y., Izutani, R., Noguchi, J., Hori, Y., Okumoto, S., Kuroda, D. Cancer Immunol. Immunother. (1995) [Pubmed]
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