Sustained activation of extracellular-signal-regulated kinase 1 (ERK1) is required for the continued expression of cyclin D1 in G1 phase

Jason D. Weber, Daniel Max Raben, Polly J. Phillips, Joseph J. Baldassare

Research output: Contribution to journalArticle

Abstract

In Chinese hamster embryo fibroblasts (IIC9 cells), platelet-derived growth factor (PDGF) stimulated mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAP kinase/ERK) activity, but not that of c-jun N-terminal kinase (JNK), and induced G1 phase progression, ERK1 activation was biphasic and was sustained throughout the G1 phase of the cell cycle. PDGF induced cyclin D1 protein and mRNA levels in a time-dependent manner. Inhibition of PDGF-induced ERK1 activity by the addition of a selective inhibitor of MEK1 (MAP kinase kinase/ERK kinase 1) activation, PD98059, or transfection with a dominant-negative ERK1 (dnERK-) was correlated with growth arrest. In contrast, growth was unaffected by expression of dominant-negative JNK (dnJNK-). Interestingly, addition of PD98059 or dnERK-, but not dnJNK-, resulted in a dramatic decrease in cyclin D1 protein and mRNA levels, concomitant with a decrease in cyclin D1-cyclin-dependent kinase activity. To investigate the importance of sustained ERK1 activation, ERK1 activity was blocked by the addition of PD98059 throughout G1. Addition of PD98059 up to 4 h after PDGF treatment decreased ERK1 activity to the levels found in growth-arrested IIC9 cells. Loss of cyclin D1 mRNA and protein expression was observed within 1 h after inhibition of the second sustained phase of ERK1 activity. Disruption of sustained ERK1 activity also resulted in G1 growth arrest. These data provide evidence for a role for sustained ERK activity in controlling G1 progression through positive regulation of the continued expression of cyclin D1, a protein known to positively regulate G1 progression.

Original languageEnglish (US)
Pages (from-to)61-68
Number of pages8
JournalBiochemical Journal
Volume326
Issue number1
StatePublished - Aug 15 1997

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Mitogen-Activated Protein Kinase 3
Cyclin D1
G1 Phase
Chemical activation
Platelet-Derived Growth Factor
JNK Mitogen-Activated Protein Kinases
Growth
Messenger RNA
Proteins
MAP Kinase Kinase Kinase 1
Cyclin-Dependent Kinases
Mitogen-Activated Protein Kinase Kinases
Extracellular Signal-Regulated MAP Kinases
Fibroblasts
Cricetulus
Mitogen-Activated Protein Kinases
Transfection
Cell Cycle
Phosphotransferases
Embryonic Structures

ASJC Scopus subject areas

  • Biochemistry

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Sustained activation of extracellular-signal-regulated kinase 1 (ERK1) is required for the continued expression of cyclin D1 in G1 phase. / Weber, Jason D.; Raben, Daniel Max; Phillips, Polly J.; Baldassare, Joseph J.

In: Biochemical Journal, Vol. 326, No. 1, 15.08.1997, p. 61-68.

Research output: Contribution to journalArticle

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