Protein kinases that phosphorylate 14-3-3 isoforms

14 -3 -3 is an abundant, predominantly phospho-binding protein, intimately involved in the regulation of many diverse signal transduction events including cell cycle regulation, nucleo-cytoplasmic targeting of essential transcription factors and regulation of catecholamine synthesis. The 14 -3 -3 family consists of 7 isoforms (denoted a, ß, y, 8, c, rl and in mammals and shows a degree of isoform specificity in binding target proteins. 14 -3 -3 is phosphorylated in an isoform specific manner, for example SDK1 /PKD phosphorylates 14 -3 -3 11,13 and (, but not cs and T. Our laboratory has previously identified in vivo 14 -3 -3 phosphorylation sites, S185 and S233. Phosphorylation of S233 by the serine /threonine protein kinase Casein kinase la (CK1 a) was shown to negatively affect the interaction with Raf kinase. The group of Gotoh have recently shown that phosphorylation of S185 by the stress activated kinase c -Jun NH2- terminal kinase (JNK) negatively effects the interaction with Bax. During studies in our laboratory that identified CKla as a 14 -3 -3 kinase, several other proteins co- purified through four steps of chromatography, including centaurin -a1 and CPI -17, suggesting a protein complex - these interactions have subsequently been characterised. CK1 has a potential phosphorylation dependent 14 -3 -3 binding site within the same region previously shown to be the interaction site for centaurin -al and the aim of this investigation was to examine the possible interaction.

Grantor dc:publisher

The University of Edinburgh

Year dc:date.issued

2006

Author dc:creator

• Clokie, Samuel J. H.

Handle dc:identifier.uri

http://hdl.handle.net/1842/30559

OAI identifier oai:identifier

oai:era.ed.ac.uk:1842/30559