Editors' ChoiceBiochemistry

New Role for 14-3-3

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Science's STKE  06 Dec 2005:
Vol. 2005, Issue 313, pp. tw432
DOI: 10.1126/stke.3132005tw432

Al-Hakim et al. explored regulation of members of the adenosine monophosphate-activated protein kinase (AMPK) family by a tandem affinity purification procedure that isolated proteins that interacted with the enzymes in cultured human embryonic kidney cells. They identified a number of new interaction partners, including the phosphoprotein-binding adaptor 14-3-3. The 14-3-3 protein interacted with the kinases QSK and SIK (salt-inducible kinase) in a manner that required their previous phosphorylation by their activating kinase LKB1. When glutathione S-transferase (GST) fusion proteins of QSK and SIK were expressed in 293 cells and affinity purified, 14-3-3 was associated with them. Displacement of 14-3-3 during incubation with a competing phosphopeptide decreased the catalytic activity of the kinases. Experiments in cells lacking LKB1 indicated that binding to 14-3-3 promoted cytoplasmic localization of QSK and SIK. Such control of protein localization is a known function of 14-3-3, but the protein has not previously been shown to directly modulate catalytic activity of its binding partners. The authors suggest that the 14-3-3 protein may work by simultaneously binding the kinases and their substrate proteins.

A. K. Al-Hakim, O. Göransson, M. Deak, R. Toth, D. G. Campbell, N. A. Morrice, A. R. Prescott, D. R. Alessi, 14-3-3 cooperates with LKB1 to regulate the activity and localization of QSK and SIK. J. Cell Sci. 118, 5661-5673 (2005). [Abstract] [Full Text]

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