Biopolym. Cell. 2001; 17(4):302-307.
Genome and Its Regulation
Isolation, expression analysis and chromosomal mapping of a novel human kinase gene MLK4
1, 2Kvasha S. M., 2, 3Protopopov A. I., 2, 3, 4Zabarovsky E. R., 1Rynditch A. V., 1, 2, 3Kashuba V. I.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Center for Genomics and Bioinformatics,
    Karolinska Institutet
    SE-171 77 Stockholm, Sweden
  3. Department of Microbiology, Tumor and Cell Biology,
    Karolinska Institute
    Nobels vag 5 171 65 Solna, Sweden
  4. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
    32, Vavilova Str., Moscow, Russian Federation, 119991


We have identified a novel human gene MLK4. Two alternatively spliced forms of MLK4, named MLKAα and β, have been isolated. The expression of MLK4 has been detected in pancreas, kidney, liver, lung, brain, placenta and heart. The gene has been mapped to chromosomal band lq42. The predicted amino acid sequence of MLK4 is highly related to the amino acid sequence of the members of MLK family, which play an important role in the signal transduction pathways.


[1] Schaeffer HJ, Weber MJ. Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol. 1999;19(4):2435-44.
[2] Yasuda J, Whitmarsh AJ, Cavanagh J, Sharma M, Davis RJ. The JIP group of mitogen-activated protein kinase scaffold proteins. Mol Cell Biol. 1999;19(10):7245-54.
[3] Treisman R. Regulation of transcription by MAP kinase cascades. Curr Opin Cell Biol. 1996;8(2):205-15.
[4] Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol. 1997;9(2):180-6.
[5] Sakuma H, Ikeda A, Oka S, Kozutsumi Y, Zanetta JP, Kawasaki T. Molecular cloning and functional expression of a cDNA encoding a new member of mixed lineage protein kinase from human brain. J Biol Chem. 1997;272(45):28622-9.
[6] Fan G, Merritt SE, Kortenjann M, Shaw PE, Holzman LB. Dual leucine zipper-bearing kinase (DLK) activates p46SAPK and p38mapk but not ERK2. J Biol Chem. 1996;271(40):24788-93.
[7] Rana A, Gallo K, Godowski P, Hirai S, Ohno S, Zon L, Kyriakis JM, Avruch J. The mixed lineage kinase SPRK phosphorylates and activates the stress-activated protein kinase activator, SEK-1. J Biol Chem. 1996;271(32):19025-8.
[8] Hirai Si, Katoh M, Terada M, Kyriakis JM, Zon LI, Rana A, Avruch J, Ohno S. MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase. J Biol Chem. 1997;272(24):15167-73.
[9] Zabarovsky ER, Allikmets R, Kholodnyuk I, Zabarovska VI, Paulsson N, Bannikov VM, Kashuba VI, Dean M, Kisselev LL, Klein G. Construction of representative NotI linking libraries specific for the total human genome and for human chromosome 3. Genomics. 1994;20(2):312-6.
[10] Sambrook J, Fritsch EF, Maniatis T. Molecular cloning: A laboratory manual. New York: Cold Spring Harbour Lab. press, 1989.
[11] Protopopov AI, Gizatullin RZ, Vorobieva NV, Protopopova MV, Kiss C, Kashuba VI, Klein G, Kisselev LL, Graphodatsky AS, Zabarovsky ER. Human chromosome 3: high-resolution fluorescence in situ hybridization mapping of 40 unique NotI linking clones homologous to genes and cDNAs. Chromosome Res. 1996;4(6):443-7.
[12] Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987;15(20):8125-48.
[13] Berthon P, Valeri A, Cohen-Akenine A, Drelon E, Paiss T, W?hr G, Latil A, Millasseau P, Mellah I, Cohen N, Blanch? H, Bellan?-Chantelot C, Demenais F, Teillac P, Le Duc A, de Petriconi R, Hautmann R, Chumakov I, Bachner L, Maitland NJ, Lidereau R, Vogel W, Fournier G, Mangin P, Cussenot O, et al. Predisposing gene for early-onset prostate cancer, localized on chromosome 1q42.2-43. Am J Hum Genet. 1998;62(6):1416-24.
[14] Launonen V, Vierimaa O, Kiuru M, Isola J, Roth S, Pukkala E, Sistonen P, Herva R, Aaltonen LA. Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc Natl Acad Sci U S A. 2001;98(6):3387-92.
[15] Hanks SK, Quinn AM, Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988;241(4861):42-52. Review.
[16] Merritt SE, Mata M, Nihalani D, Zhu C, Hu X, Holzman LB. The mixed lineage kinase DLK utilizes MKK7 and not MKK4 as substrate. J Biol Chem. 1999;274(15):10195-202.