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Sci. Signal., 26 October 2010
Vol. 3, Issue 145, p. ra78
[DOI: 10.1126/scisignal.2000738]


Editor's Summary

Sticking Together
The "master kinase" phosphoinositide-dependent kinase 1 (PDK1) plays a central role in such processes as cellular proliferation and survival and has a wide range of targets, including protein kinase B (PKB). PDK1 is downstream of phosphatidylinositol 3-kinase (PI3K), and the generation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) triggers the translocation of PDK1 and PKB to the plasma membrane, where PDK1 phosphorylates PKB. Although the mechanisms by which PDK1 activates its substrates are well studied, less is known about how the activity of PDK1 is regulated. Masters et al. used a combination of Förster resonance energy transfer (FRET)–based analysis of fluorescently tagged proteins in live cells, as well as computational modeling, to show that a subset of cytosolic PDK1 exists in a homodimeric form. Disruption of the homodimeric interface increased the association between PDK1 and PKB, and this and other evidence suggested that monomeric—rather than dimeric—PDK1 was the active form. Together, these data suggest that homodimerization of PDK1 regulates its activity.

Citation: T. A. Masters, V. Calleja, D. A. Armoogum, R. J. Marsh, C. J. Applebee, M. Laguerre, A. J. Bain, B. Larijani, Regulation of 3-Phosphoinositide–Dependent Protein Kinase 1 Activity by Homodimerization in Live Cells. Sci. Signal. 3, ra78 (2010).

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