Cloning of a human homolog of the Drosophila minibrain/rat Dyrk gene from "the Down syndrome critical region" of chromosome 21.
To isolate genes responsible for some features of Down syndrome, we performed exon trapping experiments using a series of cosmid clones derived from "the Down syndrome critical region" of chromosome 21 and isolated six exons which are highly homologous to the sequence of Drosophila minibrain (mnb) gene. The Drosophila mnb gene encodes a serine/threonine protein kinase that is required in distinct neuroblast proliferation centers during postembryonic neurogenesis. Using one of these six exons as a probe, we isolated cDNA clones for human homolog of Drosophila mnb gene (MNB) from a fetal brain cDNA library. Human MNB cDNA encodes a protein of 754 amino acids with a nuclear targeting sequence and a catalytic domain common to the serine/threonine-specific protein kinase. The human MNB protein strikingly resembles the recently discovered rat Dyrk protein kinase with a dual specificity. The MNB mRNA is expressed in various tissues including fetal and adult brains. The remarkable similarity of human MNB protein to Drosophila mnb and rat Dyrk proteins implies that human MNB protein may play a significant role in a signaling pathway regulating nuclear functions of neuronal cell proliferation, contributing to certain features of Down syndrome.
Shindoh
N
N
Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan.
Kudoh
J
J
Maeda
H
H
Yamaki
A
A
Minoshima
S
S
Shimizu
Y
Y
Shimizu
N
N
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002891:Chromosomes, Human, Pair 21; D003360:Cosmids; D017931:DNA Primers; D004314:Down Syndrome / Q000235:genetics*; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000502:physiology; D005091:Exons; D005333:Fetus; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D000097603:Dyrk Kinases
D017931:DNA Primers; D029721:Drosophila Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger; D000097603:Dyrk Kinases; C092066:mnb protein, Drosophila