Differing substrate specificities of members of the DYRK family of arginine-directed protein kinases.
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.
Campbell
Linda E
LE
Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Proud
Christopher G
CG
D000409:Alanine / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D020717:Eukaryotic Initiation Factor-2B / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation; D011392:Proline / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D012694:Serine / Q000378:metabolism; D013379:Substrate Specificity; D000097603:Dyrk Kinases
D000409:Alanine; D001120:Arginine; D020717:Eukaryotic Initiation Factor-2B; D010455:Peptides; D011392:Proline; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D012694:Serine; D000097603:Dyrk Kinases