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

Hyun Ja Nam, Sujeong Kim, Min Woo Lee, Bok Soon Lee, Toshihiro Hara, Hideyuki Saya, Hyeseong Cho, Jae Ho Lee

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1349-1358
Number of pages10
JournalCellular Signalling
Volume20
Issue number7
DOIs
Publication statusPublished - 2008 Jul

Fingerprint

Hepatocyte Growth Factor
G2 Phase
Protein Kinases
Intercellular Signaling Peptides and Proteins
Cell Cycle
Cyclin B1
Mitogen-Activated Protein Kinase Kinases
Phosphotransferases
Proto-Oncogene Proteins c-met
Ribosomal Protein S6 Kinases
Mitotic Index
Fibroblast Growth Factors
HeLa Cells
Epidermal Growth Factor
Chromosome Aberrations
Small Interfering RNA

Keywords

  • G2 delay
  • Genomic integrity
  • HGF
  • RSK

ASJC Scopus subject areas

  • Cell Biology

Cite this

The ERK-RSK1 activation by growth factors at G2 phase delays cell cycle progression and reduces mitotic aberrations. / Nam, Hyun Ja; Kim, Sujeong; Lee, Min Woo; Lee, Bok Soon; Hara, Toshihiro; Saya, Hideyuki; Cho, Hyeseong; Lee, Jae Ho.

In: Cellular Signalling, Vol. 20, No. 7, 07.2008, p. 1349-1358.

Research output: Contribution to journalArticle

Nam, Hyun Ja ; Kim, Sujeong ; Lee, Min Woo ; Lee, Bok Soon ; Hara, Toshihiro ; Saya, Hideyuki ; Cho, Hyeseong ; Lee, Jae Ho. / The ERK-RSK1 activation by growth factors at G2 phase delays cell cycle progression and reduces mitotic aberrations. In: Cellular Signalling. 2008 ; Vol. 20, No. 7. pp. 1349-1358.
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