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First published online November 23, 2005

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14-3-3 gets in the loop

14-3-3 adaptors regulate the activities of numerous proteins. By binding to phosphorylated residues within their targets, 14-3-3 can affect their localization, stability, enzyme activity and/or molecular interactions. Kinases are no exception, but on p. 5661 Abdallah Al-Hakim and co-workers reveal an entirely new way in which 14-3-3 can regulate these enzymes. The authors used a tandem affinity purification strategy to identify proteins that interact with two members of the AMP-related kinase (AMPK) family - QSK and SIK - and pulled out various 14-3-3 isoforms. They show that the interaction with 14-3-3 depends on phosphorylation of QSK/SIK by LKB1 - a tumour suppressor that activates several AMPKs - and that it does not occur in cells lacking LKB1. Significantly, the 14-3-3-binding phosphorylation site lies within the T-loop, a region critical for activity in many kinases. This has not been seen before. Al-Hakim and co-workers go on to show that binding of 14-3-3 to the phosphorylated T-loop not only enhances the catalytic activity of QSK and SIK but also regulates their localization in the cytoplasm. Finally, because many QSK/SIK substrates may themselves bind 14-3-3, the authors suggest these adaptors could function as scaffolds that facilitate interaction of the kinases and their substrates.

Related articles in JCS:

14-3-3 cooperates with LKB1 to regulate the activity and localization of QSK and SIK

Abdallah K. Al-Hakim, Olga Göransson, Maria Deak, Rachel Toth, David G. Campbell, Nick A. Morrice, Alan R. Prescott, and Dario R. Alessi
JCS 2005 118: 5661-5673. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content