In:
Journal of Cell Science, The Company of Biologists
Abstract:
Extracellular ligand stimuli control biological phenomena. Cells distinguish physiological stimuli from weak noise stimuli by establishing a ligand-concentration threshold. Hormonal control of the meiotic G2/M transition in oocytes is essential for reproduction. However, the mechanism for threshold establishment is unclear. In starfish oocytes, maturation-inducing hormones activate the PI3K-Akt pathway via Gβγ. Akt directly phosphorylates both Cdc25 and Myt1, resulting in activation of cyclin B-Cdk1, which then induces meiotic G2/M transition. Here, we show that cyclin B-Cdk1 is partially activated after subthreshold hormonal stimuli, but this triggers negative feedback (Cdk-NF), resulting in dephosphorylation of Akt sites on Cdc25 and Myt1, thereby canceling the signal. We also identified phosphatase activity for Akt substrates that exists independent of stimuli. In contrast to these negative regulatory activities, an atypical Gβγ-dependent pathway enhances PI3K-Akt-dependent phosphorylation. Based on these findings, we propose a model for threshold establishment in which hormonal dose-dependent competition between these novel pathways establishes a threshold; the atypical Gβγ-pathway becomes predominant over Cdk-NF when the stimulus exceeds this threshold. Our findings provide a regulatory connection between cell cycle and signal transduction machineries.
Type of Medium:
Online Resource
ISSN:
1477-9137
,
0021-9533
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2016
detail.hit.zdb_id:
219171-4
detail.hit.zdb_id:
1483099-1
SSG:
12
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