26 291

Cited 22 times in

The ERK-RSK1 activation by growth factors at G2 phase delays cell cycle progression and reduces mitotic aberrations.

Authors
Nam, HJ; Kim, S; Lee, MW; Lee, BS; Hara, T; Saya, H; Cho, H; Lee, JH
Citation
Cellular signalling, 20(7):1349-1358, 2008
Journal Title
Cellular signalling
ISSN
0898-65681873-3913
Abstract
Growth factors accelerate G0 to S progression in the cell cycle, however, the roles of growth factors in other cell cycle phases are largely unknown. Here, we show that treatment of HeLa cells with hepatocyte growth factor (HGF) at G2 phase induced the G2/M transition delay as evidenced by FACS analysis as well as by mitotic index and time-lapse analyses. Growth factors such as epidermal growth factor (EGF) and fibroblast growth factor (FGF) also induced G2/M transition delay like HGF. HGF treatment at G2 phase causes a delayed activation of cyclin B1-associated kinase and a diminished nuclear translocation of cyclin B1. Either U0126, a MAPK kinase (MEK) inhibitor, or kinase-dead mutant of ribosomal S6 kinase (RSK) abolished the delay. Additionally, knockdown of RSK1, but not RSK2, with siRNA abrogated the delay, indicating that the extracellular-regulated protein kinase (ERK)-RSK1 mediates the HGF-induced delay. We further found that the delay in G2/M transition of cells expressing oncogenic HGF receptor, M1268T, was abolished by RSK1 knockdown. Intriguingly, we observed that HGF induced chromosomal segregation defects, and depletion of RSK1, but not RSK2, aggravated these chromosomal aberrations. Taken together, the ERK-RSK1 activation by growth factors delays G2/M transition and this might be required to maintain genomic integrity during growth factor stimulation.
MeSH terms
CDC2 Protein Kinase/metabolismCell Cycle Proteins/metabolismChromosome Segregation/drug effectsCyclin B/metabolismCyclin B1DNA-Binding Proteins/metabolismEnzyme Activation/drug effectsExtracellular Signal-Regulated MAP Kinases/metabolism*G2 Phase/drug effects*Hela CellsHumansIntercellular Signaling Peptides and Proteins/pharmacology*Mitosis/drug effects*Mutant Proteins/metabolismProtein-Serine-Threonine Kinases/metabolismProto-Oncogene Proteins c-met/metabolismRibosomal Protein S6 Kinases, 90-kDa/metabolism*Tumor Suppressor Proteins/metabolism
DOI
10.1016/j.cellsig.2008.03.008
PMID
18450423
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
김수정조혜성이재호
Full Text Link
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse