The wee1 tyrosine kinase and cdc25 tyrosine phosphatase of fission yeast play antagonistic roles in the induction of
mitosis through cdc2 regulation. Heald et al. (1993) showed that the human wee1-like tyrosine kinase is a nuclear
protein that ensures the completion of DNA replication before mitosis in cells expressing otherwise catastrophic levels
of CDC2 activators. The human WEE1 tyrosine kinase appears to coordinate the transition between DNA replication
and mitosis by protecting the nucleus from cytoplasmically activated CDC2 kinase.
NCBI Summary:
This gene encodes a nuclear protein, which is a tyrosine kinase belonging to the Ser/Thr family of protein kinases. This protein catalyzes the inhibitory tyrosine phosphorylation of CDC2/cyclin B kinase, and appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from cytoplasmically activated CDC2 kinase. [provided by RefSeq, Jul 2008]
General function
Cell death/survival, Cell cycle regulation, DNA Replication
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Oogenesis, Oocyte maturation
Comment
Park CE, et al .
Wee1 is a kinase regulator of the M-phase promoting factor (a complex of cdc2 and cyclin B1). The present study was performed to determine the role(s) of wee1 in the early stages of mouse ovarian follicles. Expression of wee1 and the correlated cell cycle components, namely cdc2, cyclin B1, and cdc25C, was evaluated by immunohistochemistry. In addition, expression of Tyr15-phosphorylated cdc2 (cdc2-p) was also examined to determine whether wee1 kinase phosphorylates cdc2. Each component except cdc25C was found in the oocyte cytoplasm at all follicular stages, while cdc25C was not detected in primordial follicles. It was found primarily in ovarian interstitial cells and to a small extent in granulosa cells of the developing secondary follicles. To further confirm the expression of cell cycle components in the primordial follicular oocytes, day 1 ovaries were enzymatically and mechanically dissociated, then oocytes were isolated from somatic cells including pre-granulosa cells, and we confirmed that cdc2-p was expressed in oocytes of primordial follicles. The results of the present study led to the conclusion that wee1, without the counteracting cdc25C, would cause meiotic arrest of oocytes by inhibitory phosphorylation of cdc2. Expression of all these proteins in the granulosa cells of growing follicles may regulate granulosa cell mitosis concurrently with the growth of oocytes and follicles.
Expression regulated by
LH
Comment
Maturation promoting factor destabilization mediates human chorionic gonadotropin induced meiotic resumption in rat oocytes. Tiwari M et al. (2017) Human chorionic gonadotropin (hCG) mimics the action of luteinizing hormone (LH) and triggers meiotic maturation and ovulation in mammals. The mechanism by which hCG triggers meiotic resumption in mammalian oocytes remains poorly understood. We aimed to find out the impact of hCG surge on morphological changes, adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), cell division cycle 25B (Cdc25B), Wee1, early mitotic inhibitor 2 (Emi2), anaphase-promoting complex/cyclosome (APC/C), meiotic arrest deficient protein 2 (MAD2), phosphorylation status of cyclin-dependent kinase 1 (Cdk1), its activity and cyclin B1 expression levels during meiotic resumption from diplotene as well as metaphase-II (M-II) arrest in cumulus oocyte complexes (COCs). Our data suggest that hCG surge increased cyclic nucleotides level in encircling granulosa cells but decreased their level in oocyte. The reduced intraoocyte cyclic nucleotides level is associated with the decrease of Cdc25B, Thr161 phosphorylated Cdk1 and Emi2 expression levels. On the other hand, hCG surge increased Wee1, Thr14/Tyr15 phosphorylated Cdk1, APC/C as well as MAD2 expression levels. The elevated APC/C activity reduced cyclin B1 level. The changes in phosphorylation status of Cdk1 and reduced cyclin B1 level might have resulted in maturation promoting factor (MPF) destabilization. The destabilized MPF finally triggered resumption of meiosis from diplotene as well as M-II arrest in rat oocytes.//////////////////