14-3-3 phosphoprotein interaction networks – does isoform diversity present functional interaction specification?

Abstract

The 14-3-3 proteins have emerged as major phosphoprotein interaction proteins and thereby constitute a key node in the Arabidopsis Interactome Map, a node through which a large number of important signals pass. Throughout their history of discovery and description, the 14-3-3s have been described as protein families and there has been some evidence that the different 14-3-3 family members within any organism might carry isoform-specific functions. However, there has also been evidence for redundancy of 14-3-3 function, suggesting that the perceived 14-3-3 diversity may be the accumulation of neutral mutations over evolutionary time and as some 14-3-3 genes develop tissue or organ-specific expression. This situation has led to a currently unresolved question – does 14-3-3 isoform sequence diversity indicate functional diversity at the biochemical or cellular level? We discuss here some of the key observations on both sides of the resulting debate, and present a set of contrastable observations to address the theory functional diversity does exist among 14-3-3 isoforms. The resulting model suggests strongly that there are indeed functional specificities in the 14-3-3s of Arabidopsis. The model further suggests that 14-3-3 diversity and specificity should enter into the discussion of 14-3-3 roles in signal transduction and be directly approached in 14-3-3 experimentation. It is hoped that future studies involving 14-3-3s will continue to address specificity in experimental design and analysis.

Phosphorylation of HopQ1, a Type III Effector from Pseudomonas syringae, Creates a Binding Site for Host 14-3-3 Proteins

“…However, not necessarily all interactions of HopQ1 with 14-3-3s were direct, since 14-3-3s can form homodimers and heterodimers. It is often assumed that many 14-3-3 isoforms are functionally redundant, while the specificity of others can be achieved not only through protein structure but also due to distinct patterns of spatial and temporal expression, dimerization status, and phosphorylation (Boer et al, 2012;Paul et al, 2012).…”

Inhibition of the Arabidopsis Salt Overly Sensitive Pathway by 14-3-3 Proteins

“…14-3-3 proteins bind to phosphorylated proteins and transduce the phosphorylation signals to targets by affecting protein-protein interactions, protein activity, stability, conformation, and localization. Three sequence-specific motifs, RSxpSxP, RSxxpSxP, and YpT, are common phosphorylated peptides for 14-3-3 binding; however, 14-3-3 proteins also interact with proteins without these conserved motifs (Paul et al, 2012). Phosphorylation-independent interactions with 14-3-3 proteins have also been reported (Wang et al, 1999;Fuglsang et al, 2003).…”

TheArabidopsis14-3-3 Protein RARE COLD INDUCIBLE 1A Links Low-Temperature Response and Ethylene Biosynthesis to Regulate Freezing Tolerance and Cold Acclimation

“…They form homodimers and heterodimers in the native state and commonly bind to target proteins that contain specific phosphorylated motifs (Paul et al, 2012). The binding of the 14-3-3s may have different mechanistic consequences on their targets, such as conformational changes, alterations in subcellular localization, variations in intrinsic activity or stability, and changes in affinity to other proteins (Paul et al, 2012).…”