Sustained activation of the mitogen-activated protein (MAP) kinase cascade may be required for differentiation of PC12 cells. Comparison of the effects of nerve growth factor and epidermal growth factor
Open Access
- 1 December 1992
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 288 (2) , 351-355
- https://doi.org/10.1042/bj2880351
Abstract
Stimulation of PC12 cells with nerve growth factor (NGF) increased mitogen-activated protein kinase kinase (MAPKK) activity > 20-fold after 5 min to a level that was largely sustained for at least 90 min. MAPKK activity was stimulated to a similar level by epidermal growth factor (EGF), but peaked at 2 min, declining thereafter and returning to basal levels after 60-90 min. Activation of MAPKK by either growth factor occurred prior to the activation of MAP kinase, consistent with MAPKK being the physiological activator of MAP kinase. The results demonstrate that the transient activation of MAPKK by EGF and its sustained activation by NGF underlies the transient and sustained activation of MAP kinase induced by EGF and NGF respectively. NGF or EGF induced the same two forms of MAPKK that were resolved on a Mono Q column. The Peak-1 MAPKK was activated initially and partially converted into the more acidic peak-2 MAPKK after prolonged growth-factor stimulation. The Peak-2 MAPKK was 20-fold more sensitive to inactivation by the catalytic subunit of protein phosphatase 2A. Stimulation with NGF caused a striking translocation of MAP kinase from the cytosol to the nucleus after 30 min, but not nuclear translocation of MAP kinase occurred after stimulation with EGF. The results suggest that sustained activation of the MAP kinase cascade may be required for MAP kinase to enter the nucleus, where it may initiate the gene transcription events required for neuronal differentiation of PC12 cells.Keywords
This publication has 16 references indexed in Scilit:
- MAP kinase kinase from rabbit skeletal muscle A novel dual specificity enzyme showing homology to yeast protein kinases involved in pheromone‐dependent signal transductionFEBS Letters, 1992
- Nuclear localization and regulation of erk- and rsk-encoded protein kinases.Molecular and Cellular Biology, 1992
- ERKs: A family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGFCell, 1991
- Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase).1991
- Multiple components in an epidermal growth factor-stimulated protein kinase cascade. In vitro activation of a myelin basic protein/microtubule-associated protein 2 kinase.1991
- Microtubule‐associated‐protein (MAP) kinase activated by nerve growth factor and epidermal growth factor in PC12 cellsEuropean Journal of Biochemistry, 1990
- Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinaseNature, 1990
- Insulin-stimulated MAP-2 kinase phosphorylates and activates ribosomal protein S6 kinase IINature, 1988
- Primary-structure requirements for inhibition by the heat-stable inhibitor of the cAMP-dependent protein kinase.Proceedings of the National Academy of Sciences, 1986
- Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.Proceedings of the National Academy of Sciences, 1976