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

Campbell, Linda E. and Proud, Christopher G. (2002) Differing substrate specificities of members of the DYRK family of arginine-directed protein kinases. FEBS Letters, 510 (1-2), 31-36. (doi:10.1016/S0014-5793(01)03221-5).

Record type: Article

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 ?-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.

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