Regulation
In S. pombe, Wee1 is phosphorylated
Cdk1 and cyclin B make up the maturation promoting factor (MPF) which promotes the entry into mitosis. It is inactivated by phosphorylation through Wee1 and activated by the phosphatase Cdc25C. Cdc25C in turn is activated by Polo kinase and inactivated by Chk1. Thus in S. pombe Wee1 regulation is mainly under the control of phosphorylation through the polarity kinase, Pom1's, pathway including Cdr2 and Cdr1.
At the G2/M transition, Cdk1 is activated by Cdc25 through dephosphorylation of Tyr15. At the same time, Wee1 is inactivated through phosphorylation at its C-terminal catalytic domain by Nim1/Cdr1. Also, the active MPF will promote its own activity by activating Cdc25 and inactivating Wee1, creating a positive feedback loop, though this is not yet understood in detail.
Higher eukaryotes regulate Wee1 via phosphorylation and degradation
In higher eukaryotes, Wee1 inactivation occurs both by phosphorylation and degradation. The protein complex SCFβ-TrCP1/2 is an E3 ubiquitin ligase that functions in Wee1A ubiquitination. The M-phase kinases Polo-like kinase (Plk1) and Cdc2 phosphorylate two serine residues in Wee1A which are recognized by SCFβ-TrCP1/2.
S. cerevisiae homologue Swe1
In S. cerevisiae, cyclin-dependent kinase Cdc28 (Cdk1 homologue) is phosphorylated by Swe1 (Wee1 homologue) and dephosphorylated by Mih1 (Cdc25 homologue). Nim1/Cdr1 homologue in S. cerevisiae, Hsl1, together with its related kinases Gin4 and Kcc4 localize Swe1 to the bud-neck. Bud-neck associating kinases Cla4 and Cdc5 (polo kinase homologue) phosphorylate Swe1 at different stages of the cell cycle. Swe1 is also phosphorylated by Clb2-Cdc28 which serves as a recognition for further phosphorylation by Cdc5.
The S. cerevisiae protein Swe1 is also regulated by degradation. Swe1 is hyperphosphorylated by Clb2-Cdc28 and Cdc5 which may be a signal for ubiquitination and degradation by SCF E3 ubiquitin ligase complex as in higher eukaryotes.
Read more about this topic: Wee1
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