NKIAMRE, a novel conserved CDC2-related kinase with features of both mitogen-activated protein kinases and cyclin-dependent kinases.
We report the cloning of the NKIAMRE gene located on human chromosome 5q31.1. It encodes a novel 52kDa Cdc2-related kinase with a 1.5kb open reading frame. Like MAP kinases, NKIAMRE contains a Thr-X-Tyr (TXY) motif in the activation loop domain. Similar to cdks, NKIAMRE contains the putative negative regulatory Ser14 and Tyr15 residues and the cyclin-binding motif, NKIAMRE, from which it derives its name. Human NKIAMRE has significant amino acid identity to related kinases in rat, mouse, Caenorhabditis elegans, and Drosophila, and is widely expressed in human tissues and cell lines. Confocal microscopy demonstrates that NKIAMRE localizes to the cytoplasm. NKIAMRE is activated by treatment of cells with phorbol 12-myristate 13-acetate. Mutation of the ATP-binding Lys-33 to arginine and the Thr-Glu-Tyr motif to Ala-Glu-Phe abolished its ability to phosphorylate myelin basic protein. NKIAMRE is a member of a conserved family of kinases with homology to both MAP kinases and cyclin-dependent kinases.
Yee
Karen W L
KW
Department of Medical Biophysics, University of Toronto, Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, Ont., Canada M5G 2M9. kyee@uhnres.utoronto.ca
Moore
Susan J
SJ
Midmer
Michael
M
Zanke
Brent W
BW
Tong
Frances
F
Hedley
David
D
Minden
Mark D
MD
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000737:chemistry* / Q000502:physiology*; D019556:COS Cells; D002895:Chromosomes, Human, Pair 5; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D015723:Gene Library; D005822:Genetic Vectors; D006801:Humans; D008239:Lysine / Q000737:chemistry; D020935:MAP Kinase Signaling System; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D004676:Myelin Basic Protein / Q000737:chemistry; D009206:Myocardium / Q000378:metabolism; D016366:Open Reading Frames; D010766:Phosphorylation; D010802:Phylogeny; D011233:Precipitin Tests; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry; D013755:Tetradecanoylphorbol Acetate / Q000737:chemistry; D014018:Tissue Distribution; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D004676:Myelin Basic Protein; D020033:Protein Isoforms; D012694:Serine; D001120:Arginine; C477873:CDKL3 protein, human; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D008239:Lysine; D013755:Tetradecanoylphorbol Acetate