Differing substrate specificities of members of the DYRK family of arginine-directed protein kinases

FEBS Lett. 2002 Jan 2;510(1-2):31-6. doi: 10.1016/s0014-5793(01)03221-5.

Abstract

The mammalian DYRK (dual specificity tyrosine phosphorylated and regulated kinase) family of protein kinases comprises a number of related, but poorly understood enzymes. DYRK1A is nuclear while DYRKs 2 and 3 are cytoplasmic. We recently showed that DYRK2 phosphorylates the translation initiation factor eIF2B at Ser539 in its epsilon-subunit and thereby "primes" its phosphorylation by glycogen synthase kinase-3. Here we have used peptides based on the sequence around Ser539 to help define the specificity of DYRK2/3 in comparison with DYRK1A. These kinases require an arginine N-terminal to the target residue for efficient substrate phosphorylation. This cannot be replaced even by lysine. A peptide with arginine at -2 is phosphorylated much less well by all three kinases than one with arginine at -3. Replacement of the +1 proline by alanine almost completely eliminates substrate phosphorylation, but valine here does allow phosphorylation especially by DYRK2. This study reveals both similarities and differences in the specificities of these arginine-dependent protein kinases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / metabolism
  • Animals
  • Arginine / metabolism*
  • Eukaryotic Initiation Factor-2B / metabolism*
  • Peptides / metabolism
  • Phosphorylation
  • Proline / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism*
  • Rats
  • Serine / metabolism
  • Substrate Specificity

Substances

  • Eukaryotic Initiation Factor-2B
  • Peptides
  • Serine
  • Arginine
  • Proline
  • Dyrk kinase
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • Alanine