Cloning of a human homolog of the Drosophila minibrain/rat Dyrk gene from 'the Down syndrome critical region' of chromosome 21

Nobuaki Shindoh, Jun Kudoh, Hideto Maeda, Akiko Yamaki, Shinsei Minoshima, Yoshiko Shimizu, Nobuyoshi Shimizu

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)92-99
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume225
Issue number1
DOIs
Publication statusPublished - 1996 Aug 5

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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