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Gene Review

NRK  -  Nik related kinase

Homo sapiens

Synonyms: DKFZp686A17109, Nik-related protein kinase
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Disease relevance of NRK

  • We have isolated a strongly mitogenic, type beta transforming growth factor (beta TGF) released by Snyder-Theilen feline sarcoma virus-transformed rat embryo (FeSV-Fre) cells that induces phenotypic transformation of normal NRK cells when they are concomitantly stimulated by analogues of epidermal growth factor (EGF) [1].
  • In contrast, E2 had no effect on the induction of CAT activity in the preosteoblastic cell lines RCT-1 and TRAB-11, in the rat osteosarcoma cell line ROS 17/2.8, and in the fibroblastic cell lines BALB-c/3T3 and NRK [2].
  • Furthermore, rat GC-conditioned medium contained much more TGF beta activity than medium from normal rat kidney cells (NRK 49-F), human prostatic adenocarcinoma cells (PC-3), or porcine GC [3].
  • Progressive deletion constructs of both the promoters have been made using a PCR based approach and the basal promoter activities studied in Xenopus tadpole cell line (XTC), Xenopus adult kidney fibroblast cell line (A6), human hepatoma cell line (HepG2), normal rat kidney cell line (NRK), and Chinese hamster ovary cell line (CHO) [4].
  • Tendon fibroblasts were significantly more resistant to hyperthermia than NRK 49F cells after 30, 45 and 60 min of heating and significantly more resistant than dermal fibroblasts after 45 and 60 min of heating [5].

High impact information on NRK


Chemical compound and disease context of NRK


Biological context of NRK


Anatomical context of NRK


Associations of NRK with chemical compounds

  • PTHrP increased cAMP formation in RCB 2.2 cells but not in NIH 3T3 or NRK 49F cells [22].
  • A growth-factor-like substance capable of inducing nontransformed mouse AKR-2B, rat NRK, and EGF-receptorless mouse NR6 cells to form progressively growing colonies in soft agar was identified in acid/ethanol extracts of 17-day mouse embryos [23].
  • In NRK cells either transfected with mutated adducin or incubated with 10(-9) M OU, PST normalizes the Na-K pump activity [11].
  • MTT reduction to formazan was the most sensitive in the NRK cell line [24].
  • We have compared the effects of ATR in freshly isolated renal proximal tubules and glomeruli from rat and also in cell lines: NRK, derived from the proximal tubules, and MDBK and MDCK more closely representing the distal nephron [24].

Regulatory relationships of NRK

  • Although more active in radioreceptor assay than in radioimmunoassay, the EGF-competing factor is distinct from TGF alpha or beta since it is unable to induce anchorage-independent growth of NRK or FR3T3 target cells in the presence or absence of exogenous EGF [25].
  • These results show that the relative potency of the three PDGF isoforms to stimulate proliferation of NRK cells is different for quiescent cells in monolayer, density-arrested cells and anchorage-independent cells [26].

Other interactions of NRK

  • Levels of endogenous progastrin-derived peptides were modified by stable transfection of NRK cells with tetracycline-repressible plasmids containing sequences encoding human gastrin in either the sense or antisense orientation [27].
  • Fourteen out of thirty extracts were scored positive for TGF-beta in the NRK colony forming assay and these tumours presented at an earlier clinical stage and were predominantly well differentiated [28].
  • This pattern of localization of the endogenous protein was similar to the localization of ARF6 when overexpressed in NRK, or HeLa, cells [20].
  • In NRK cells, hsp70 was clearly induced by conditioning treatments (42 degrees C for 2 h, 45 degrees C for 15 min or 100 microM sodium arsenite for 1 h) [29].
  • NRK cell clones highly reduced in the Raf-1 production are generated by the expression of a c-raf-1 antisense RNA [30].

Analytical, diagnostic and therapeutic context of NRK


  1. Type beta transforming growth factor from feline sarcoma virus-transformed rat cells. Isolation and biological properties. Massagué, J. J. Biol. Chem. (1984) [Pubmed]
  2. Functional estrogen receptors in osteoblastic cells demonstrated by transfection with a reporter gene containing an estrogen response element. Ernst, M., Parker, M.G., Rodan, G.A. Mol. Endocrinol. (1991) [Pubmed]
  3. The production of transforming growth factor-beta activity by rat granulosa cell cultures. Kim, I.C., Schomberg, D.W. Endocrinology (1989) [Pubmed]
  4. Comparative functional analysis of rat TGF-beta1 and Xenopus laevis TGF-beta5 promoters suggest differential regulations. Goswami, M.T., Desai, K.V., Kondaiah, P. J. Mol. Evol. (2003) [Pubmed]
  5. The effect of exercise-induced localised hyperthermia on tendon cell survival. Birch, H.L., Wilson, A.M., Goodship, A.E. J. Exp. Biol. (1997) [Pubmed]
  6. A link between cyclin A expression and adhesion-dependent cell cycle progression. Guadagno, T.M., Ohtsubo, M., Roberts, J.M., Assoian, R.K. Science (1993) [Pubmed]
  7. Induction of heparin-binding epidermal growth factor-like growth factor mRNA in rat kidney after acute injury. Homma, T., Sakai, M., Cheng, H.F., Yasuda, T., Coffey, R.J., Harris, R.C. J. Clin. Invest. (1995) [Pubmed]
  8. Connexin-occludin chimeras containing the ZO-binding domain of occludin localize at MDCK tight junctions and NRK cell contacts. Mitic, L.L., Schneeberger, E.E., Fanning, A.S., Anderson, J.M. J. Cell Biol. (1999) [Pubmed]
  9. Tubular early endosomal networks in AtT20 and other cells. Tooze, J., Hollinshead, M. J. Cell Biol. (1991) [Pubmed]
  10. Identification of a 52-kD calmodulin-binding protein associated with the mitotic spindle apparatus in mammalian cells. Brady, R.C., Cabral, F., Dedman, J.R. J. Cell Biol. (1986) [Pubmed]
  11. Antihypertensive compounds that modulate the Na-K pump. Ferrari, P., Ferrandi, M., Torielli, L., Barassi, P., Tripodi, G., Minotti, E., Molinari, I., Melloni, P., Bianchi, G. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  12. Comparative cytotoxicity of 5-aminosalicylic acid (mesalazine) and related compounds in different cell lines. Noble, E., Janssen, L., Dierickx, P.J. Cell Biol. Toxicol. (1997) [Pubmed]
  13. Prodigiosin-induced apoptosis in human colon cancer cells. Montaner, B., Pérez-Tomás, R. Life Sci. (2001) [Pubmed]
  14. NESK, a member of the germinal center kinase family that activates the c-Jun N-terminal kinase pathway and is expressed during the late stages of embryogenesis. Nakano, K., Yamauchi, J., Nakagawa, K., Itoh, H., Kitamura, N. J. Biol. Chem. (2000) [Pubmed]
  15. Cofilin phosphorylation and actin polymerization by NRK/NESK, a member of the germinal center kinase family. Nakano, K., Kanai-Azuma, M., Kanai, Y., Moriyama, K., Yazaki, K., Hayashi, Y., Kitamura, N. Exp. Cell Res. (2003) [Pubmed]
  16. Apoptosis induced by microinjection of cytochrome c is caspase-dependent and is inhibited by Bcl-2. Brustugun, O.T., Fladmark, K.E., Doskeland, S.O., Orrenius, S., Zhivotovsky, B. Cell Death Differ. (1998) [Pubmed]
  17. Subcellular localization of LGN during mitosis: evidence for its cortical localization in mitotic cell culture systems and its requirement for normal cell cycle progression. Kaushik, R., Yu, F., Chia, W., Yang, X., Bahri, S. Mol. Biol. Cell (2003) [Pubmed]
  18. Dihydroceramide biology. Structure-specific metabolism and intracellular localization. Kok, J.W., Nikolova-Karakashian, M., Klappe, K., Alexander, C., Merrill, A.H. J. Biol. Chem. (1997) [Pubmed]
  19. Growth inhibition by vaccinia virus growth factor. Lin, Y.Z., Ke, X.H., Tam, J.P. J. Biol. Chem. (1990) [Pubmed]
  20. Localization of endogenous ARF6 to sites of cortical actin rearrangement and involvement of ARF6 in cell spreading. Song, J., Khachikian, Z., Radhakrishna, H., Donaldson, J.G. J. Cell. Sci. (1998) [Pubmed]
  21. Delayed cyclin A and B1 degradation in non-transformed mammalian cells. Girard, F., Fernandez, A., Lamb, N. J. Cell. Sci. (1995) [Pubmed]
  22. Growth factor-like properties of parathyroid hormone-related peptide in transfected rodent cell line. Li, X., Drucker, D.J. Cancer Res. (1993) [Pubmed]
  23. Mouse embryos contain polypeptide growth factor(s) capable of inducing a reversible neoplastic phenotype in nontransformed cells in culture. Proper, J.A., Bjornson, C.L., Moses, H.L. J. Cell. Physiol. (1982) [Pubmed]
  24. Selective cytotoxicity associated with in vitro exposure of fresh rat renal fragments and continuous cell lines to atractyloside. Obatomi, D.K., Bach, P.H. Arch. Toxicol. (1996) [Pubmed]
  25. Simultaneous production of IGF-I and EGF competing growth factors by HT-29 human colon cancer line. Culouscou, J.M., Remacle-Bonnet, M., Garrouste, F., Marvaldi, J., Pommier, G. Int. J. Cancer (1987) [Pubmed]
  26. Differential effects of PDGF isoforms on proliferation of normal rat kidney cells. Van Zoelen, E.J., Van Rotterdam, W., Van de Wetering, R.A., Heldin, C.H. Growth Factors (1993) [Pubmed]
  27. Overexpression of sense or antisense human gastrin mRNA does not affect proliferation of normal rat kidney fibroblasts. Yang, Z., Paterson, A., Karelina, Y., Zhang, Q.X., Shulkes, A., Baldwin, G.S. Int. J. Biochem. Cell Biol. (1999) [Pubmed]
  28. Bioassay of transforming growth factor-beta activity in acidic protein extracts from primary breast cancer specimens. Godden, J., Porteous, C., George, W.D., Kerr, D.J. Anticancer Res. (1993) [Pubmed]
  29. Development of thermotolerance in hsp70 induction-defective mutant of NRK cells. Sakakibara, Y., Shimada, Y., Masuda, A., Ohtsuka, K. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. (1992) [Pubmed]
  30. Raf-1 protein kinase is an integral component of the oncogenic signal cascade shared by epidermal growth factor and platelet-derived growth factor. Kizaka-Kondoh, S., Sato, K., Tamura, K., Nojima, H., Okayama, H. Mol. Cell. Biol. (1992) [Pubmed]
  31. Epithelial tissue-derived growth factor-like polypeptides. Halper, J., Moses, H.L. Cancer Res. (1983) [Pubmed]
  32. An endogenous carbohydrate-binding protein of baby hamster kidney (BHK21 C13) cells. Temporal changes in cellular expression in the developing kidney. Foddy, L., Stamatoglou, S.C., Hughes, R.C. J. Cell. Sci. (1990) [Pubmed]
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