14-3-3 binding regulates catalytic activity of human Wee1 kinase.
14-3-3 binding regulates catalytic activity of human Wee1 kinase.
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发表时间：
2001-12
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通讯作者：
Cynthia J. Rothblum-Oviatt;C. Ryan;H. Piwnica-Worms
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作者：
Cynthia J. Rothblum-Oviatt;C. Ryan;H. Piwnica-Worms
有丝分裂诱导剂Cdc 2负调控，部分，酪氨酸15磷酸化。人Wee 1是一种酪氨酸特异性蛋白激酶，磷酸化酪氨酸15上的Cdc 2。人Wee 1受到多个水平的调节，包括可逆磷酸化、蛋白水解和蛋白质-蛋白质相互作用。在这里，我们研究了14-3-3结合人类Wee 1的调节和功能所作的贡献。我们报告说，14-3-3蛋白与人Wee 1的相互作用在有丝分裂过程中减少，并在蛋白激酶抑制剂UCN-01的存在下稳定。不能与14-3-3蛋白结合的Wee 1突变体具有较低的酶活性，这可能是其在体内过量产生时诱导G（2）细胞周期延迟的效力相对于野生型Wee 1降低的原因。这些发现表明，14-3-3蛋白作为人类Wee 1蛋白激酶的正调节剂发挥作用。
The mitotic inducer Cdc2 is negatively regulated, in part, by phosphorylation on tyrosine 15. Human Wee1 is a tyrosine-specific protein kinase that phosphorylates Cdc2 on tyrosine 15. Human Wee1 is subject to multiple levels of regulation including reversible phosphorylation, proteolysis, and protein-protein interactions. Here we have investigated the contributions made by 14-3-3 binding to human Wee1 regulation and function. We report that the interactions of 14-3-3 proteins with human Wee1 are reduced during mitosis and are stable in the presence of the protein kinase inhibitor UCN-01. A mutant of Wee1 that is incapable of binding to 14-3-3 proteins has lower enzymatic activity, and this likely accounts for its reduced potency relative to wild-type Wee1 in inducing a G(2) cell cycle delay when overproduced in vivo. These findings indicate that 14-3-3 proteins function as positive regulators of the human Wee1 protein kinase.