14-3-3 binding regulates catalytic activity of human Wee1 kinase.
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.
Mesh Terms:
14-3-3 Proteins, Adenoviridae, Animals, Blotting, Western, Catalysis, Cell Cycle, Cell Cycle Proteins, Escherichia coli, G2 Phase, HeLa Cells, Humans, Mitosis, Nuclear Proteins, Phosphorylation, Protein Binding, Protein Structure, Tertiary, Protein-Tyrosine Kinases, Time Factors, Transfection, Tyrosine 3-Monooxygenase
14-3-3 Proteins, Adenoviridae, Animals, Blotting, Western, Catalysis, Cell Cycle, Cell Cycle Proteins, Escherichia coli, G2 Phase, HeLa Cells, Humans, Mitosis, Nuclear Proteins, Phosphorylation, Protein Binding, Protein Structure, Tertiary, Protein-Tyrosine Kinases, Time Factors, Transfection, Tyrosine 3-Monooxygenase
Cell Growth Differ
Date: Dec. 01, 2001
PubMed ID: 11751453
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