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Gene Review

ALPK1  -  alpha-kinase 1

Homo sapiens

Synonyms: 8430410J10Rik, Alpha-protein kinase 1, Chromosome 4 kinase, FLJ22670, KIAA1527, ...
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Disease relevance of ALPK1

  • HLA class I-restricted EBV-specific cytotoxicity was shown in interleukin-2-dependent cultures from 3 of 3 EBV- tumors, whereas cultures from 6 of 6 EBV+ tumors were either noncytotoxic or exerted LAK-type cytotoxicity [1].
  • Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients [2].
  • These data show a reciprocal interaction between DCs and NK/LAK cells, leading to the amplification of NK cell effector functions, and support the implementation of DC/NK cell-based immunotherapy for purging the graft and/or controlling minimal residual disease after autologous stem cell transplantation [2].
  • In an effort to stimulate in vivo LAK cell activity at relatively nontoxic doses, 20 patients with advanced metastatic malignancy (13 renal cell carcinoma, 6 melanoma, 1 lymphoma) were treated with recombinant human interleukin-2 (IL-2) by continuous 5-day splenic artery perfusion using the femoral approach [3].
  • Their LAK activity against Daudi cells was 66.2 +/- 13.1% and 48.7 +/- 12.7% against self glioma cells, 54.4 +/- 10.1% against K562 cells, 43.1 +/- 7.9% against Raji cells, and 33.5 +/- 16.2% against allogeneic glioma cells [4].

Psychiatry related information on ALPK1


High impact information on ALPK1

  • Furthermore, anti-beta treatment of the K562 and A549 tumor cell lines inhibited NK (by > 95%) and interleukin 2-activated killer (LAK) cell (by 75%) cytotoxicity, respectively [7].
  • This technique not only provides a novel method for the purification of LGL/NK cells for in vitro studies but also provides a means for the rapid expansion of highly purified cells with high levels of broad antitumor (LAK) cytotoxicity [8].
  • From the experiments of negative selection with mAbs and complements, these newly developed killer cells after chemotherapy were thought to be LAK-like cells [9].
  • These rapidly expanding LGL/NK cells also generated very high levels of LAK activity (including lysis of fresh NK-resistant solid tumor cells), expressed a phenotype characteristic of activated rat NK/LAK cells, and incorporated [3H]TdR into DNA [8].
  • Clonogenic assay demonstrated a fivefold to 10-fold reduction in the surviving fraction of tumor cells with doxorubicin but no change with LAK/rIL-2.(ABSTRACT TRUNCATED AT 250 WORDS)[10]

Chemical compound and disease context of ALPK1

  • The sensitivity of tumor cells to lysis by natural killer (NK) and interleukin-2 (IL-2)-activated killer (LAK) cells was studied in three ovarian carcinoma cell lines (2780.9S, SKOV-3, and CHOAUXB1), four multidrug-resistant (MDR) variants, and a melphalan-resistant line [11].
  • Cisplatin induces fas expression in esophageal cancer cell lines and enhanced cytotoxicity in combination with LAK cells [12].
  • A positive correlation between the sensitivity to LAK and the ID50 for doxorubicin (Dx) was found in 44 melanoma clones analyzed, suggesting that spontaneously drug-resistant clones have a higher sensitivity to LAK than the drug-sensitive clones [13].
  • Staurosporine and pertussis toxin, which slightly suppressed LAK induction, did not inhibit tyrosine phosphorylation of the 105-110 kDa protein [14].
  • We have also seen, however, that steroid medications used by patients to control their cerebral edema may depress the anti-tumor activity of rIL-2 by depressing the capacity of lymphocytes to develop normal LAK activity [15].

Biological context of ALPK1


Anatomical context of ALPK1

  • The expression of ALPK1 increases by the time of epithelial cell differentiation, whereas the intracellular localization of ALPK1 on apical transport vesicles was confirmed by confocal analysis [16].
  • After incubation for 4 days with IL-2 (1 U/ml), purified lymphocytes showed maximal LAK activity against NK cell-resistant target (Daudi) cells, as assessed by 4-hour 51Cr release assay [19].
  • Direct comparison of equal numbers of CML ALAK cells and a CML LAK cell population produced by incubation of peripheral blood mononuclear cells in rIL-2 for 14 days without adherence revealed that the CML LAK population had significantly lower lytic activity against K562 and Raji cell lines [20].
  • At a concentration of 4-HC commonly used for BM purging (60 micrograms/mL), there were 4 to 5 logs of T-cell depletion and almost complete elimination of NK- and LAK-cell activity [21].
  • The CML ALAK population is relatively homogeneous, not contaminated with viable stem cells, not derived from a malignant lineage, and more cytotoxic than equal numbers of CML LAK cells [20].

Associations of ALPK1 with chemical compounds


Analytical, diagnostic and therapeutic context of ALPK1

  • The combinational use of IFN-gamma and anti-CD3 x anti-tumor BsAb might be a promising way of enhancing LAK cell-mediated adoptive immunotherapy in small cell lung cancer patients [26].
  • Splenic artery perfusion with IL-2 can result in significant in vivo peripheral LAK cell generation as well as enhancement of I-LAK and NK activity that persists at least 16 days after the cessation of treatment [3].
  • AMs, obtained by bronchoalveolar lavage from healthy volunteers, or peripheral blood monocytes were added to a standard 4-h chromium release LAK assay at varying concentrations [27].
  • Following chronic treatment with intramuscular injections of IL2 at 1 x 10(6) units/m2, we observed augmentation of peripheral blood natural killer activity and induction of peripheral blood LAK activity [28].
  • Ten patients were treated with a protocol of 5-day i.v. rIL-2 bolus priming (10(5) units/kg, every 8 h), followed by 5 daily phereses with harvested lymphocytes cultured in vitro to generate LAK, and 5 days of rIL-2 bolus with infusion of LAK cells [29].


  1. Local suppression of Epstein-Barr virus (EBV)-specific cytotoxicity in biopsies of EBV-positive Hodgkin's disease. Frisan, T., Sjöberg, J., Dolcetti, R., Boiocchi, M., De Re, V., Carbone, A., Brautbar, C., Battat, S., Biberfeld, P., Eckman, M. Blood (1995) [Pubmed]
  2. Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients. Valteau-Couanet, D., Leboulaire, C., Maincent, K., Tournier, M., Hartmann, O., Bénard, J., Beaujean, F., Boccaccio, C., Zitvogel, L., Angevin, E. Blood (2002) [Pubmed]
  3. In vivo induction of lymphokine-activated killer cells by interleukin-2 splenic artery perfusion in advanced malignancy. Klasa, R.J., Silver, H.K., Kong, S. Cancer Res. (1990) [Pubmed]
  4. Local administration of autologous lymphokine-activated killer cells and recombinant interleukin 2 to patients with malignant brain tumors. Yoshida, S., Tanaka, R., Takai, N., Ono, K. Cancer Res. (1988) [Pubmed]
  5. Crisis intervention after the Tsunami in Phuket and Khao Lak. Bronisch, T., Maragkos, M., Freyer, C., Müller-Cyran, A., Butollo, W., Weimbs, R., Platiel, P. Crisis. (2006) [Pubmed]
  6. Alteration in body image for the patient undergoing RIL-2/LAK cell therapy. Becker, K., Koutlas, J. Oncology nursing forum. (1990) [Pubmed]
  7. A novel ligand in lymphocyte-mediated cytotoxicity: expression of the beta subunit of H+ transporting ATP synthase on the surface of tumor cell lines. Das, B., Mondragon, M.O., Sadeghian, M., Hatcher, V.B., Norin, A.J. J. Exp. Med. (1994) [Pubmed]
  8. Lymphokine-activated killer cells in rats. III. A simple method for the purification of large granular lymphocytes and their rapid expansion and conversion into lymphokine-activated killer cells. Vujanovic, N.L., Herberman, R.B., Maghazachi, A.A., Hiserodt, J.C. J. Exp. Med. (1988) [Pubmed]
  9. Induction of lymphokine-activated killer-like cells by cancer chemotherapy. Kiyohara, T., Taniguchi, K., Kubota, S., Koga, S., Sakuragi, T., Saitoh, Y. J. Exp. Med. (1988) [Pubmed]
  10. Secondary screening system for preclinical testing of human lung cancer therapies. Mulvin, D.W., Howard, R.B., Mitchell, D.H., Noker, P.E., Kruse, C.A., Chu, H.D., Bunn, P.A., Johnston, M.R. J. Natl. Cancer Inst. (1992) [Pubmed]
  11. P-glycoprotein-mediated multidrug resistance and lymphokine-activated killer cell susceptibility in ovarian carcinoma. Savas, B., Cole, S.P., Tsuruo, T., Pross, H.F. J. Clin. Immunol. (1996) [Pubmed]
  12. Cisplatin induces fas expression in esophageal cancer cell lines and enhanced cytotoxicity in combination with LAK cells. Matsuzaki, I., Suzuki, H., Kitamura, M., Minamiya, Y., Kawai, H., Ogawa, J. Oncology (2000) [Pubmed]
  13. Susceptibility of human and murine drug-resistant tumor cells to the lytic activity of rIL2-activated lymphocytes (LAK). Gambacorti-Passerini, C., Rivoltini, L., Radrizzani, M., Supino, R., Mariani, M., Parmiani, G. Cancer Metastasis Rev. (1988) [Pubmed]
  14. NK-LAK induction with IL-2 is regulated by tyrosine phosphorylation of a 105-110 kDa protein. Yoneda, K., Osaki, T. Immunobiology (1994) [Pubmed]
  15. Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes. A review of pre-clinical and clinical investigations. Merchant, R.E., Ellison, M.D., Young, H.F. J. Neurooncol. (1990) [Pubmed]
  16. Alpha-kinase 1, a new component in apical protein transport. Heine, M., Cramm-Behrens, C.I., Ansari, A., Chu, H.P., Ryazanov, A.G., Naim, H.Y., Jacob, R. J. Biol. Chem. (2005) [Pubmed]
  17. Effects of human alveolar macrophages on the induction of lymphokine (IL 2)-activated killer cells. Sone, S., Utsugi, T., Nii, A., Ogura, T. J. Immunol. (1987) [Pubmed]
  18. Protection of cultured human monocytes from lymphokine-activated killer-mediated lysis by IFN-gamma. Blanchard, D.K., Djeu, J.Y. J. Immunol. (1988) [Pubmed]
  19. Differential effects of recombinant interferons alpha, beta, and gamma on induction of human lymphokine (IL-2)-activated killer activity. Sone, S., Utsugi, T., Nii, A., Ogura, T. J. Natl. Cancer Inst. (1988) [Pubmed]
  20. Adherent lymphokine-activated killer cells in chronic myelogenous leukemia: a benign cell population with potent cytotoxic activity. Verfaillie, C., Miller, W., Kay, N., McGlave, P. Blood (1989) [Pubmed]
  21. Differential effect of 4-hydroperoxycyclophosphamide and antimyeloid monoclonal antibodies on T and natural killer cells during bone marrow purging. Zhong, R.K., Donnenberg, A.D., Rubin, J., Ball, E.D. Blood (1994) [Pubmed]
  22. Heterogeneity of long-term cultured activated killer cells induced by anti-T3 antibody. Yun, Y.S., Hargrove, M.E., Ting, C.C. J. Immunol. (1988) [Pubmed]
  23. The high lysability by LAK cells of colon-carcinoma cells resistant to doxorubicin is associated with a high expression of ICAM-1, LFA-3, NCA and a less-differentiated phenotype. Rivoltini, L., Cattoretti, G., Arienti, F., Mastroianni, A., Melani, C., Colombo, M.P., Parmiani, G. Int. J. Cancer (1991) [Pubmed]
  24. Up- and down-regulation of human lymphokine (IL-2)-activated killer cell induction by monocytes, depending on their functional state. Nii, A., Sone, S., Utsugi, T., Yanagawa, H., Ogura, T. Int. J. Cancer (1988) [Pubmed]
  25. Ex vivo purging of allogeneic marrow with L-Leucyl-L-leucine methyl ester. A phase I study. Rosenfeld, C.S., Thiele, D.L., Shadduck, R.K., Zeigler, Z.R., Schindler, J. Transplantation (1995) [Pubmed]
  26. Induction of intercellular adhesion molecule 1 on small cell lung carcinoma cell lines by gamma-interferon enhances spontaneous and bispecific anti-CD3 x antitumor antibody-directed lymphokine activated killer cell cytotoxicity. Azuma, A., Yagita, H., Matsuda, H., Okumura, K., Niitani, H. Cancer Res. (1992) [Pubmed]
  27. Inhibition of lymphokine-activated killer cell function by human alveolar macrophages. Roth, M.D., Golub, S.H. Cancer Res. (1989) [Pubmed]
  28. Immunomodulatory properties and toxicity of interleukin 2 in patients with cancer. Urba, W.J., Steis, R.G., Longo, D.L., Kopp, W.C., Maluish, A.E., Marcon, L., Nelson, D.L., Stevenson, H.C., Clark, J.W. Cancer Res. (1990) [Pubmed]
  29. Circulating cytokines in patients with metastatic cancer treated with recombinant interleukin 2 and lymphokine-activated killer cells. Gemlo, B.T., Palladino, M.A., Jaffe, H.S., Espevik, T.P., Rayner, A.A. Cancer Res. (1988) [Pubmed]
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