Mechanism for inactivation of the mitotic inhibitory kinase Wee1 at M phase
- 6 March 2007
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (10), 3753-3758
- https://doi.org/10.1073/pnas.0607357104
Abstract
Wee1, the inhibitory kinase of cyclin B/Cdc2, undergoes a phosphorylation-dependent catalytic inactivation at M phase of the mitotic cell cycle, but the precise mechanism for this inactivation is not known. Using Xenopus egg and extract systems, we show here that the kinase activity of Xenopus somatic Wee1 (XeWee1B) is regulated by its N-terminal, small, well conserved region, termed here the Wee-box. The Wee-box is essential for the normal kinase activity of XeWee1B during interphase, acting positively on the C-terminal catalytic domain, which alone cannot efficiently phosphorylate Cdc2. Significantly, a Thr-186-Pro (TP) motif within the Wee-box is phosphorylated by Cdc2 at M phase and specifically binds the cis/trans prolyl isomerase Pin1. This Pin1 binding is required for the inactivation of XeWee1B at M phase, presumably causing isomerization of the phospho-TP motif and thereby impairing the function of the Wee-box. These results provide important insights into the mechanism of Wee1 inactivation at M phase.This publication has 27 references indexed in Scilit:
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