Mechanism for inactivation of the mitotic inhibitory kinase Wee1 at M phase.
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.
Okamoto
Kengo
K
Department of Biology, Graduate School of Sciences, Kyushu University, Hakozaki 6-10-1, Fukuoka 812-8581, Japan.
Sagata
Noriyuki
N
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D002455:Cell Division; D005786:Gene Expression Regulation; D007313:Insecta; D008938:Mitosis; D008969:Molecular Sequence Data; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009865:Oocytes / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism*
D018797:Cell Cycle Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D029867:Xenopus Proteins; C466028:Wee2 protein, Xenopus; D011505:Protein-Tyrosine Kinases; D019696:Peptidylprolyl Isomerase