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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.
- Source :
-
The Biochemical journal [Biochem J] 1997 Aug 15; Vol. 326 ( Pt 1), pp. 61-8. - Publication Year :
- 1997
-
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.
- Subjects :
- Animals
Calcium-Calmodulin-Dependent Protein Kinases antagonists & inhibitors
Calcium-Calmodulin-Dependent Protein Kinases physiology
Cell Division drug effects
Cell Line
Cricetinae
Cricetulus
Enzyme Activation drug effects
Fibroblasts
Flavonoids pharmacology
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 3
Platelet-Derived Growth Factor pharmacology
Time Factors
Up-Regulation drug effects
Calcium-Calmodulin-Dependent Protein Kinases metabolism
Cyclin D1 biosynthesis
G1 Phase drug effects
Mitogen-Activated Protein Kinases
Subjects
Details
- Language :
- English
- ISSN :
- 0264-6021
- Volume :
- 326 ( Pt 1)
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 9337851
- Full Text :
- https://doi.org/10.1042/bj3260061