Does Isoform Diversity Explain Functional Differences in the 14-3-3Protein Family?

E.      Kjarland; T.   J.   Keen; R.      Kleppe

doi:10.2174/138920106777549777

Abstract

The 14-3-3 family of proteins was originally identified in 1967 as simply an abundant brain protein. However ittook almost 25 years before the ubiquitous role of 14-3-3 in cell biology was recognized when it was found to interactwith several signalling and proto-oncogene proteins. Subsequently 14-3-3 proteins were the first protein recognized tobind a discrete phosphoserine/threonine-binding motifs. In mammals the 14-3-3 protein family is comprised of seven ho-mologous isoforms. The 14-3-3 family members are expressed in all eukaryotes and although no single conserved func-tion of the 14-3-3s is apparent, their ability to bind other proteins seems a crucial characteristic. To date more than 300binding partners have been identified, of which most are phosphoproteins. Consequently, it has become clear that 14-3-3proteins are involved in the regulation of most cellular processes, including several metabolic pathways, redox-regulation,transcription, RNA processing, protein synthesis, protein folding and degradation, cell cycle, cytoskeletal organization andcellular trafficking. In this review we include recent reports on the regulation of 14-3-3 by phosphorylation, and discussthe possible functional significance of the existence of distinct 14-3-3 isoforms in light of recent proteomics studies. Inaddition we discuss 14-3-3 interaction as a possible drug target.

Keywords: 14-3-3, protein-protein interaction, phosphorylation, isoform diversity, signal transduction, proteomics

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