First published online November 23, 2005
Journal of Cell Science 118, 2305e (2005)
© The Company of Biologists Limited
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.

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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.
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