The University of Southampton
University of Southampton Institutional Repository

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

Differing substrate specificities of members of the DYRK family of arginine-directed protein kinases
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 ?-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.
protein kinase, DYRK, proline, minbrain, initiation factor, eIF
0014-5793
31-36
Campbell, Linda E.
371996b8-6fec-4559-a379-eddd322ab09d
Proud, Christopher G.
59dabfc8-4b44-4be8-a17f-578a58550cb3
Campbell, Linda E.
371996b8-6fec-4559-a379-eddd322ab09d
Proud, Christopher G.
59dabfc8-4b44-4be8-a17f-578a58550cb3

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.

This record has no associated files available for download.

More information

Submitted date: 18 July 2001
Published date: 2 January 2002
Keywords: protein kinase, DYRK, proline, minbrain, initiation factor, eIF

Identifiers

Local EPrints ID: 56408
URI: http://eprints.soton.ac.uk/id/eprint/56408
ISSN: 0014-5793
PURE UUID: 73d30fe8-8e17-4d12-955f-c27452f28938

Catalogue record

Date deposited: 07 Aug 2008
Last modified: 15 Mar 2024 11:01

Export record

Altmetrics

Contributors

Author: Linda E. Campbell
Author: Christopher G. Proud

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×