Measurement of Wee Kinase Activity

Mueller, Paul R.; Leise, Walter F.

doi:10.1385/1-59259-857-9:299

Cited by 7 publications

(7 citation statements)

References 34 publications

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“…The direct Cdk1/CycB regulation consists of two independent mechanisms. First, inhibitory phosphorylation occurs at Thr14 and Tyr15 [ 43 , 44 ]. Importantly, the phosphorylation of Cdk1/CycB at Thr161 of the Cdk subunit by Cdk activating kinase (CAK) is a prerequisite for the activation of the Cdk/Cyc complex [ 45 , 46 ].…”

Section: Physiological Role Of Wee Family Kinasesmentioning

confidence: 99%

Regulation of G2/M Transition by Inhibition of WEE1 and PKMYT1 Kinases

et al. 2017

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In the cell cycle, there are two checkpoint arrests that allow cells to repair damaged DNA in order to maintain genomic integrity. Many cancer cells have defective G1 checkpoint mechanisms, thus depending on the G2 checkpoint far more than normal cells. G2 checkpoint abrogation is therefore a promising concept to preferably damage cancerous cells over normal cells. The main factor influencing the decision to enter mitosis is a complex composed of Cdk1 and cyclin B. Cdk1/CycB is regulated by various feedback mechanisms, in particular inhibitory phosphorylations at Thr14 and Tyr15 of Cdk1. In fact, Cdk1/CycB activity is restricted by the balance between WEE family kinases and Cdc25 phosphatases. The WEE kinase family consists of three proteins: WEE1, PKMYT1, and the less important WEE1B. WEE1 exclusively mediates phosphorylation at Tyr15, whereas PKMYT1 is dual-specific for Tyr15 as well as Thr14. Inhibition by a small molecule inhibitor is therefore proposed to be a promising option since WEE kinases bind Cdk1, altering equilibria and thus affecting G2/M transition.

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Section: Physiological Role Of Wee Family Kinasesmentioning

confidence: 99%

Regulation of G2/M Transition by Inhibition of WEE1 and PKMYT1 Kinases

et al. 2017

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“…WEE1B, a newly identified member of the WEE1 kinase family, is conserved from yeast to humans and has recently been shown to suppress CDK1 activity by phosphorylating its inhibitory sites (16)(17)(18)(19)(20)(21). While WEE1A and PKMYT1 are well documented as important regulators of mitosis in multiple cell types in numerous species (22), the role and regulation of WEE1B in zygotes and early embryo development remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Ser 15 of WEE1B is a potential PKA phosphorylation target in G2/M transition in one-cell stage mouse embryos

Liu¹,

Liu²,

Wu³

et al. 2013

Molecular Medicine Reports

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The WEE1 kinase family has been shown to be the major kinase family responsible for phosphorylating Tyr 15 on cyclin-dependent kinase 1 (CDK1). WEE1 homolog 2 (WEE2, also known as WEE1B) was first identified in Xenopus laevis and more recently in humans and mice, and is responsible for phosphorylating the CDK1 inhibitory site and maintaining meiotic arrest in oocytes. However, the mechanism by which WEE1B is regulated in one-cell stage mouse embryos remains to be elucidated. In the present study, we examined the role of WEE1B-Ser 15 in G2/M transition of one-cell stage mouse embryos. WEE1B-Ser 15 was phosphorylated during the G1 and S phases, whereas Ser 15 was dephosphorylated during G2 and M phases in vivo. Overexpression of the phosphor-mimic Wee1B-S15D mutant delayed the re-entry of embryos into mitosis more efficiently than Wee1B-wild type (Wee1B-WT) by direct phosphorylation of CDK1-Tyr 15. The results of the present study suggested that WEE1B acts as a direct downstream substrate of protein kinase A (PKA) and that Ser 15 of WEE1B is a potential PKA phosphorylation target in the G2/M transition of mouse embryos. In addition, WEE1B inhibits mitosis by negatively regulating M phase promoting factor activity in one-cell stage mouse embryos.

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“…Cdc2 (also termed Cdk1) and its regulator cyclin B drive cells into mitosis from G 2 phase. In early G2 phase, Cdk1 is inactivated by phosphorylation of T14 and Y15 residues by Wee1 and Myt1 kinases [ 60 ]. The initial activation of cyclin B/Cdk1 occurs at the centrosome in prophase.…”

Section: Introductionmentioning

confidence: 99%

Centrosome-associated regulators of the G2/M checkpoint as targets for cancer therapy

et al. 2009

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In eukaryotic cells, control mechanisms have developed that restrain cell-cycle transitions in response to stress. These regulatory pathways are termed cell-cycle checkpoints. The G 2 /M checkpoint prevents cells from entering mitosis when DNA is damaged in order to afford these cells an opportunity to repair the damaged DNA before propagating genetic defects to the daughter cells. If the damage is irreparable, checkpoint signaling might activate pathways that lead to apoptosis. Since alteration of cell-cycle control is a hallmark of tumorigenesis, cell-cycle regulators represent potential targets for therapy. The centrosome has recently come into focus as a critical cellular organelle that integrates G 2 /M checkpoint control and repairs signals in response to DNA damage. A growing number of G 2 /M checkpoint regulators have been found in the centrosome, suggesting that centrosome has an important role in G 2 /M checkpoint function. In this review, we discuss centrosome-associated regulators of the G 2 /M checkpoint, the dysregulation of this checkpoint in cancer, and potential candidate targets for cancer therapy.

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Measurement of Wee Kinase Activity

Cited by 7 publications

References 34 publications

Regulation of G2/M Transition by Inhibition of WEE1 and PKMYT1 Kinases

Regulation of G2/M Transition by Inhibition of WEE1 and PKMYT1 Kinases

Ser 15 of WEE1B is a potential PKA phosphorylation target in G2/M transition in one-cell stage mouse embryos

Centrosome-associated regulators of the G2/M checkpoint as targets for cancer therapy

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