AI Article Synopsis
- 14-3-3 proteins regulate various cellular processes in eukaryotes by binding to phosphorylated proteins, emphasizing the impact of their self-dimerization.
- A study showed that most 14-3-3-associated proteins in COS-7 cells are phosphorylated in a way detectable by a specific antibody, highlighting the importance of dimerization for proper binding to these phosphoproteins.
- The research found that dimerization enhances 14-3-3's ability to bind to phosphorylated targets like Raf and DAF-16, while also decreasing 14-3-3's likelihood of being phosphorylated itself, suggesting a balance between these two processes.
Article Abstract
14-3-3 proteins via binding serine/threonine-phosphorylated proteins regulate diverse intracellular processes in all eukaryotic organisms. Here, we examine the role of 14-3-3 self-dimerization in target binding, and in the susceptibility of 14-3-3 to undergo phosphorylation. Using a phospho-specific antibody developed against a degenerated mode-1 14-3-3 binding motif (RSxpSxP), we demonstrate that most of the 14-3-3-associated proteins in COS-7 cells are phosphorylated on sites that react with this antibody. The binding of these phosphoproteins depends on 14-3-3 dimerization, inasmuch as proteins associated in vivo with a monomeric 14-3-3 form are not recognized by the phospho-specific antibody. The role of 14-3-3 dimerization in the phosphorylation-dependent target binding is further exemplified with two well-defined 14-3-3 targets, Raf and DAF-16. Raf and DAF-16 can bind both monomeric and dimeric 14-3-3; however, whereas phosphorylation of specific Raf and DAF-16 sites is required for binding to dimeric 14-3-3, binding to monomeric 14-3-3 forms is entirely independent of Raf and DAF-16 phosphorylation. We also find that dimerization diminishes 14-3-3 susceptibility to phosphorylation. These findings establish a significant role of 14-3-3 dimerization in its ability to bind targets in a phosphorylation-dependent manner and point to a mechanism in which 14-3-3 phosphorylation and dimerization counterregulate each other.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC266786 | PMC |
| http://dx.doi.org/10.1091/mbc.e02-12-0821 | DOI Listing |
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Article Synopsis
- 14-3-3 proteins regulate various cellular processes in eukaryotes by binding to phosphorylated proteins, emphasizing the impact of their self-dimerization.
- A study showed that most 14-3-3-associated proteins in COS-7 cells are phosphorylated in a way detectable by a specific antibody, highlighting the importance of dimerization for proper binding to these phosphoproteins.
- The research found that dimerization enhances 14-3-3's ability to bind to phosphorylated targets like Raf and DAF-16, while also decreasing 14-3-3's likelihood of being phosphorylated itself, suggesting a balance between these two processes.
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