dDYRK2: a novel dual-specificity tyrosine-phosphorylation-regulated kinase in Drosophila

Biochem J. 2003 Sep 1;374(Pt 2):381-91. doi: 10.1042/BJ20030500.

Abstract

Dual-specificity tyrosine-phosphorylation-regulated kinases (DYRKs) are an emerging family of protein kinases that have been identified in all eukaryotic organisms examined to date. DYRK family members are involved in regulating key developmental and cellular processes such as neurogenesis, cell proliferation, cytokinesis and cellular differentiation. Two distinct subgroups exist, nuclear and cytosolic. In Drosophila, the founding family member minibrain, whose human orthologue maps to the Down syndrome critical region, belongs to the nuclear subclass and affects post-embryonic neurogenesis. In the present paper, we report the isolation of dDYRK2, a cytosolic DYRK and the putative product of the smell-impaired smi35A gene. This is the second such kinase described in Drosophila, but the first to be characterized at the molecular and biochemical level. dDYRK2 is an 81 kDa dual-specificity kinase that autophosphorylates on tyrosine and serine/threonine residues, but appears to phosphorylate exogenous substrates only on serine/threonine residues. It contains a YXY motif in the activation loop of the kinase domain in the same location as the TXY motif in mitogen-activated protein kinases. dDYRK2 is tyrosine-phosphorylated in vivo, and mutational analysis reveals that the activation loop tyrosines are phosphorylated and are essential for kinase activity. Finally, dDYRK2 is active at all stages of fly development, with elevated levels observed during embryogenesis and pupation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Enzyme Activation
  • Gene Expression Regulation, Developmental / genetics
  • Histones / metabolism
  • Molecular Sequence Data
  • Myelin Basic Protein / metabolism
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / chemistry*
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / biosynthesis
  • Protein-Tyrosine Kinases / chemistry*
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Substrate Specificity / genetics

Substances

  • Drosophila Proteins
  • Histones
  • Myelin Basic Protein
  • Phosphoproteins
  • Recombinant Proteins
  • Phosphotyrosine
  • Dyrk kinase
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases

Associated data

  • GENBANK/AF168467