Cytokinesis regulator ECT2 changes its conformation through phosphorylation at Thr-341 in G2/M phase
Open Access
- 19 September 2005
- journal article
- research article
- Published by Springer Nature in Oncogene
- Vol. 25 (4), 566-578
- https://doi.org/10.1038/sj.onc.1209078
Abstract
The Rho activator ECT2 functions as a key regulator in cytokinesis. ECT2 is phosphorylated during G2/M phase, but the physiological significance of this event is not well known. In this study, we show that phosphorylation of ECT2 at threonine-341 (T341) affects the autoregulatory mechanism of ECT2. In G2/M phase, ECT2 was phosphorylated at T341 most likely by Cyclin B/Cyclin-dependent kinase 1 (Cdk1), and then dephosphorylated before cytokinesis. Depletion of ECT2 by RNA interference (RNAi) efficiently induced multinucleate cells. Expression of the phospho-deficient mutant of ECT2 at T341 suppressed the multinucleation induced by RNAi to ECT2, indicating that ECT2 is biologically active even when it is not phosphorylated at T341. However, the phospho-mimic mutation at T341 weakly stimulates the catalytic activity of ECT2 as detected by serum response element reporter gene assays. As T341 is located at the hinge region of the N-terminal regulatory domain and C-terminal catalytic domain, phosphorylation of T341 may help accessing downstream signaling molecules to further activate ECT2. We found that the phospho-mimic mutation T341D increases binding with itself or the N-terminal half of ECT2. These results suggest a conformational change of ECT2 upon phosphorylation at T341. Therefore, ECT2 activity might be regulated by the phosphorylation status of T341. We propose that T341 phosphorylation by Cyclin B/Cdk1 could be a trigger for further activation of ECT2.Keywords
This publication has 26 references indexed in Scilit:
- Cell Type-specific Regulation of RhoA Activity during CytokinesisJournal of Biological Chemistry, 2004
- Nucleotide Exchange Factor ECT2 Interacts with the Polarity Protein Complex Par6/Par3/Protein Kinase Cζ (PKCζ) and Regulates PKCζ ActivityMolecular and Cellular Biology, 2004
- The Polo-Box Domain: A Molecular Integrator of Mitotic Kinase Cascades and Polo-like Kinase FunctionCell Cycle, 2004
- Rho exchange factor ECT2 is induced by growth factors and regulates cytokinesis through the N‐terminal cell cycle regulator‐related domainsJournal of Cellular Biochemistry, 2003
- Targets of the cyclin-dependent kinase Cdk1Nature, 2003
- Cell Cycle-Regulated Phosphorylation of p21-Activated Kinase 1Current Biology, 2002
- Accumulation of GTP-bound RhoA during Cytokinesis and a Critical Role of ECT2 in This AccumulationJournal of Biological Chemistry, 2000
- Human Ect2 Is an Exchange Factor for Rho Gtpases, Phosphorylated in G2/M Phases, and Involved in CytokinesisThe Journal of cell biology, 1999
- Distinct expression patterns and transforming properties of multiple isoforms of Ost, an exchange factor for RhoA and Cdc42Oncogene, 1999
- Oncogene ect2 is related to regulators of small GTP-binding proteinsNature, 1993