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Sci. Signal., 22 December 2009
Vol. 2, Issue 102, p. ec406
[DOI: 10.1126/scisignal.2102ec406]

EDITORS' CHOICE

Biochemistry Solving Pseudokinases

L. Bryan Ray

Science, Science Signaling, AAAS, Washington, DC 20005, USA

An unusual activation mechanism is described by Zeqiraj et al. for the activation of the protein kinase LKB1, mutations of which are associated with cancer in humans. Many kinases are activated by phosphorylation, but a protein that activates LKB1, STRAD{alpha}, is a pseudokinase—a protein with similarity to protein kinases that binds ATP but does not phosphorylate substrates. The crystal structure of an activating complex containing LKB shows that STRAD{alpha} works with another protein, MO25{alpha}, to hold LKB1 in an active conformation. The results demonstrate a mechanism that may help explain the evolutionary origin of pseudokinases, the biological roles of other pseudokinases, and the mechanisms of disease-causing mutations in LKB1.

E. Zeqiraj, B. M. Filippi, M. Deak, D. R. Alessi, D. M. F. van Aalten, Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation. Science 326, 1707–1711 (2009). [Abstract] [Full Text]

Citation: L. B. Ray, Solving Pseudokinases. Sci. Signal. 2, ec406 (2009).

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