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Gene Review

IK  -  IK cytokine, down-regulator of HLA II

Homo sapiens

Synonyms: CSA2, Cytokine IK, IK factor, Protein RER, Protein Red, ...
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Disease relevance of IK


Psychiatry related information on IK

  • METHODS: A total of 2417 men and 384 women were measured for VO2max by indirect calorimetry (RER > 1.1); age (yr); gender by M = 1, W = 0; self-report activity habit by the 11-point (0-10) NASA physical activity status scale (PASS); WG at the apex of the umbilicus; %fat by skinfolds; and BMI by weight (kg) divided by height squared (m) [5].
  • The results obtained in this study suggest that RER alleviates memory deficits via receptor-mediated events, and that short APP-derived peptides might represent a novel group of therapeutically active molecules for the alleviation of memory deficits in age-related dementias [6].

High impact information on IK

  • Rabbit blood monocytes, which contain no cytochemically demonstrable peroxidase, develop peroxidatic activity in the RER and perinuclear cisternae within 2 h after adherence to serum- or fibrin-coated surfaces [7].
  • Nystatin was employed to selectively permeabilize the basolateral or apical membrane to determine the effect of ibuprofen on apical Cl- (ICl) and basolateral K+ (IK) currents after stimulation by forskolin [8].
  • Based on topological studies mannosylphosphoryldolichol (Man-P-Dol) is synthesized on the cytoplasmic face of the RER, but functions as a mannosyl donor in Glc3Man9GlcNAc2-P-P-dolichol biosynthesis after the mannosyl-phosphoryl headgroup diffuses transversely to the luminal compartment [9].
  • Traffic between the RER and the Golgi stack as outlined by ssHRPKDEL occurs via vesicular carriers as well as by tubular elements. ssHRP has also been used to investigate the trans side of the Golgi complex, where incubation at reduced temperatures outlines the trans-Golgi network with HRP reaction product [10].
  • This confirmed that the PB were formed within the RER and that the Golgi complex was not involved in their transport to vacuoles [11].

Chemical compound and disease context of IK

  • RESULTS: Preincubation of platinum-resistant A2780 human ovarian cancer cells with CSA 2 micrograms/mL significantly enhanced CBDCA cytotoxicity in clonogenic assays [12].
  • Cell lines that constitutively express herpes simplex virus 1 (HSV-1) glycoprotein H (gH-1) failed to synthesize the mature form of gH and accumulated a precursor-like form of the glycoprotein, which was retained intracellularly, most likely in RER [13].
  • The presence of malignant appearing tumor cells with abundant and dilated cisternae of RER, in an intercellular matrix containing collagen fibers with areas of focal collections or puffs of hydroxyapatite crystals, are the most characteristic ultrastructural features of osteosarcoma [14].
  • In rats fed ethanol and a nutritionally adequate diet including corn oil (25% of calories) by intragastric cannula for five months the fatty liver progressed to focal central fibrosis, and Ito cell activation (fat/RER) was increased [15].

Biological context of IK

  • IK expression increased and was therefore inversely correlated with the gradual loss of HLA-DR during growth factor-induced CD34+ cell proliferation and differentiation [16].
  • To study the possible role of IK in hematopoiesis, antisense probes were used [16].
  • IK gene localization shows that it maps on chromosome 2p15-p14 [17].
  • Here, we demonstrate a novel role for IK in MHC class II expression since over-expression of this protein by stable transfection into human B cells led to a total disappearance of constitutive MHC class II mRNA expression [18].
  • An important physiological role of IK channels is to set the membrane potential at fairly negative values and thereby to build up large electrical gradients for the passive transport of ions such as Cl- efflux driving water and Na+ secretion from epithelia, and Ca2+ influx controlling T-lymphocyte proliferation [2].

Anatomical context of IK

  • The current study demonstrates that IK gene transcripts are present in CD34+ cells purified from human umbilical cord blood [16].
  • We have purified a cytokine (IK factor, 19 kDa) secreted by the leukemic cell line K562 and several cancer cells, which inhibits HLA Class II antigen induction by IFN-gamma [17].
  • This review discusses the Ca2+-activated K+ channels of intermediate conductance (IK channels), and their historical discovery in erythrocytes, their classical biophysical characteristics, physiological function, molecular biology as well as their role as possible molecular targets for pharmacological intervention in various diseases [2].
  • IK channels are involved in the regulatory volume decrease in human epithelial cells [19].
  • Patch clamp methods were used to study calcium activated (IKCa) and voltage-gated (IK) potassium currents in enzymatically disassociated hair cells from the saccule of the toadfish Opsanus tau [20].

Associations of IK with chemical compounds

  • IK expression was specifically inhibited by an antisense oligodeoxynucleotide containing two phosphorothioate internucleotide linkages at each of the 3' and 5' ends and corresponding to the initiation site of IK mRNA [16].
  • Moreover, in Colo 205, HLA-DR can also be induced by the protein synthesis inhibitor Cycloheximide (0.1 micrograms ml-1); and addition of IK factor almost completely abolishes HLA class II expression [17].
  • The IK channel is potently blocked by the scorpion toxin charybdotoxin (ChTx) and the antimycotic clotrimazole (CLT) [2].
  • The niflumic acid-stimulated IK was reversed by subsequent application of iberiotoxin or paxilline, yet not by that of glibenclamide or apamin [21].
  • RESULTS: In MG-63 cells, niflumic acid and meclofenamic acid increased K+ outward currents (IK) [21].

Regulatory relationships of IK

  • Taken together these results demonstrate that the IK protein plays a key role in the constitutive expression of MHC class II antigens and that inhibition induced by IK is upstream of CIITA in this regulatory pathway [18].

Other interactions of IK

  • Implication of a new molecule IK in CD34+ hematopoietic progenitor cell proliferation and differentiation [16].
  • These results provide evidence that the IK molecule participates in the regulation of HLA-DR expression on hematopoietic cells and plays a role in growth factor-dependent CD34+ cell proliferation and differentiation by modulating HLA-DR expression [16].
  • Examination of CIITA mRNA in IK stably transfected clones revealed a marked reduction of CIITA mRNA transcription [18].
  • Inhibitor (IK) of IFN-gamma induced HLA class II antigens expression also inhibits HLA class II constitutive expression in the human Raji B cell line [18].
  • The recent cloning of the human IK channel gene (KCNN4) enabled a detailed mapping of the expression in various tissues [2].

Analytical, diagnostic and therapeutic context of IK

  • The molecular cloning of IK and SK channels has revealed that both channels gain their Ca2+-sensitivity from tightly bound calmodulin (CaM) [2].
  • By quantitative RT-PCR, we could show that MiaPaCa-2 cells exhibit a 2.8-fold and BxPC3 cells a more than 8-fold elevated level of IK mRNA level compared with PANC-1 cells [3].
  • The properties of a quickly inactivating transient K current (IA) and a slowly inactivating delayed K current (IK) were investigated with two-electrode voltage-clamp techniques in the isolated soma of the Retzius cell of the leech, Macrobdella decora [22].
  • Western blots from the external muscle revealed an immunoreactive band at the molecular weight of the IK channel [4].
  • Gel filtration and cross-linking data showed that RER-localized invariant chain is present as trimers or aggregated trimers [23].


  1. The interferon inhibiting cytokine IK is overexpressed in cutaneous T cell lymphoma derived tumor cells that fail to upregulate major histocompatibility complex class II upon interferon-gamma stimulation. Willers, J., Häffner, A., Zepter, K., Storz, M., Urosevic, M., Burg, G., Dummer, R. J. Invest. Dermatol. (2001) [Pubmed]
  2. The Ca2+-activated K+ channel of intermediate conductance: a molecular target for novel treatments? Jensen, B.S., Strøbaek, D., Olesen, S.P., Christophersen, P. Current drug targets. (2001) [Pubmed]
  3. Blockage of intermediate-conductance Ca2+-activated K+ channels inhibit human pancreatic cancer cell growth in vitro. Jäger, H., Dreker, T., Buck, A., Giehl, K., Gress, T., Grissmer, S. Mol. Pharmacol. (2004) [Pubmed]
  4. Intermediate conductance potassium (IK) channels occur in human enteric neurons. Furness, J.B., Kearney, K., Robbins, H.L., Hunne, B., Selmer, I.S., Neylon, C.B., Chen, M.X., Tjandra, J.J. Autonomic neuroscience : basic & clinical. (2004) [Pubmed]
  5. Nonexercise models for estimating VO2max with waist girth, percent fat, or BMI. Wier, L.T., Jackson, A.S., Ayers, G.W., Arenare, B. Medicine and science in sports and exercise. (2006) [Pubmed]
  6. Amyloid precursor protein: from synaptic plasticity to Alzheimer's disease. Mileusnic, R., Lancashire, C.L., Rose, S.P. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  7. Appearance of peroxidase reactivity within the rough endoplasmic reticulum of blood monocytes after surface adherence. Bodel, P.T., Nichols, B.A., Bainton, D.F. J. Exp. Med. (1977) [Pubmed]
  8. Ibuprofen inhibits cystic fibrosis transmembrane conductance regulator-mediated Cl- secretion. Devor, D.C., Schultz, B.D. J. Clin. Invest. (1998) [Pubmed]
  9. Transmembrane movement of a water-soluble analogue of mannosylphosphoryldolichol is mediated by an endoplasmic reticulum protein. Rush, J.S., Waechter, C.J. J. Cell Biol. (1995) [Pubmed]
  10. Transport into and out of the Golgi complex studied by transfecting cells with cDNAs encoding horseradish peroxidase. Connolly, C.N., Futter, C.E., Gibson, A., Hopkins, C.R., Cutler, D.F. J. Cell Biol. (1994) [Pubmed]
  11. Evidence for a novel route of wheat storage proteins to vacuoles. Levanony, H., Rubin, R., Altschuler, Y., Galili, G. J. Cell Biol. (1992) [Pubmed]
  12. Phase I trial of carboplatin and infusional cyclosporin in advanced malignancy. Morgan, R.J., Margolin, K., Raschko, J., Akman, S., Leong, L., Somlo, G., Scanlon, K., Ahn, C., Carroll, M., Doroshow, J.H. J. Clin. Oncol. (1995) [Pubmed]
  13. Herpes simplex virus (HSV) glycoprotein H is partially processed in a cell line that expresses the glycoprotein and fully processed in cells infected with deletion or ts mutants in the known HSV glycoproteins. Foà-Tomasi, L., Avitabile, E., Boscaro, A., Brandimarti, R., Gualandri, R., Manservigi, R., Dall'Olio, F., Serafini-Cessi, F., Fiume, G.C. Virology (1991) [Pubmed]
  14. The ultrastructure of conventional, parosteal, and periosteal osteosarcomas. Martínez-Tello, F.J., Navas-Palacios, J.J. Cancer (1982) [Pubmed]
  15. Ito cell activation induced by chronic ethanol feeding in the presence of different dietary fats. French, S.W., Takahashi, H., Wong, K., Mendenhall, C.L. Alcohol and alcoholism (Oxford, Oxfordshire). Supplement. (1991) [Pubmed]
  16. Implication of a new molecule IK in CD34+ hematopoietic progenitor cell proliferation and differentiation. Cao, L.X., Le Bousse-Kerdiles, M.C., Clay, D., Oshevski, S., Jasmin, C., Krief, P. Blood (1997) [Pubmed]
  17. A new cytokine (IK) down-regulating HLA class II: monoclonal antibodies, cloning and chromosome localization. Krief, P., Augery-Bourget, Y., Plaisance, S., Merck, M.F., Assier, E., Tanchou, V., Billard, M., Boucheix, C., Jasmin, C., Azzarone, B. Oncogene (1994) [Pubmed]
  18. Inhibitor (IK) of IFN-gamma induced HLA class II antigens expression also inhibits HLA class II constitutive expression in the human Raji B cell line. Vedrenne, J., Assier, E., Pereno, R., Bouzinba-Segard, H., Azzarone, B., Jasmin, C., Charron, D., Krief, P. Oncogene (1997) [Pubmed]
  19. IK channels are involved in the regulatory volume decrease in human epithelial cells. Wang, J., Morishima, S., Okada, Y. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  20. Characterization of voltage-gated and calcium-activated potassium currents in toadfish saccular hair cells. Steinacker, A., Romero, A. Brain Res. (1991) [Pubmed]
  21. Fenamates stimulate BKCa channel osteoblast-like MG-63 cells activity in the human. Wu, S.N., Jan, C.R., Chiang, H.T. J. Investig. Med. (2001) [Pubmed]
  22. Transient and delayed potassium currents in the Retzius cell of the leech, Macrobdella decora. Johansen, J., Kleinhaus, A.L. J. Neurophysiol. (1986) [Pubmed]
  23. Invariant chain trimers are sequestered in the rough endoplasmic reticulum in the absence of association with HLA class II antigens. Marks, M.S., Blum, J.S., Cresswell, P. J. Cell Biol. (1990) [Pubmed]
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