Abstract
Signals activating the kinases that phosphorylate neurofilament proteins in the axon remain unknown. In a previous study, we have demonstrated that a constitutively active form of MEK1 activates Erk1 and Erk2 kinases, which phosphorylate co-transfected NF-M in NIH 3T3 cells. In this study, we report the activation of endogenous Erk1 and Erk2 by membrane depolarization and calcium influx through L-type calcium channels, which resulted in phosphorylation of the NF-M tail domain in PC12 cells. This phosphorylation was inhibited in the presence of nifedipine, an L-type calcium channel inhibitor, and PD98059, a specific MEK1 inhibitor. Our data suggest a mechanism linking calcium influx through voltage-gated calcium channels with the MAP kinase pathway and NF-M tail domain phosphorylation in cell body and neurite. These findings may provide significant new insights into mechanisms involved in some neurological diseases.
Copyright 1999 Published by Elsevier Science B.V.
MeSH terms
-
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
-
Animals
-
Calcium / metabolism*
-
Calcium Channel Agonists / pharmacology
-
Calcium Channel Blockers / pharmacology
-
Calcium Channels / drug effects
-
Calcium Channels / metabolism*
-
Calcium Channels, L-Type
-
Calcium Signaling / physiology*
-
Calcium-Calmodulin-Dependent Protein Kinases / genetics
-
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
-
Cell Membrane / physiology*
-
Enzyme Inhibitors / pharmacology
-
Flavonoids / pharmacology
-
Ion Channel Gating / drug effects
-
Ion Transport / drug effects
-
Membrane Potentials*
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3
-
Mitogen-Activated Protein Kinases*
-
Neoplasm Proteins / metabolism
-
Nerve Tissue Proteins / metabolism*
-
Neurites / ultrastructure
-
Neurofilament Proteins / metabolism*
-
Nifedipine / pharmacology
-
PC12 Cells
-
Phosphorylation
-
Protein Processing, Post-Translational*
-
Rats
-
Recombinant Fusion Proteins / metabolism
-
Transfection
Substances
-
Calcium Channel Agonists
-
Calcium Channel Blockers
-
Calcium Channels
-
Calcium Channels, L-Type
-
Enzyme Inhibitors
-
Flavonoids
-
Neoplasm Proteins
-
Nerve Tissue Proteins
-
Neurofilament Proteins
-
Recombinant Fusion Proteins
-
neurofilament protein M
-
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
-
Calcium-Calmodulin-Dependent Protein Kinases
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3
-
Mitogen-Activated Protein Kinases
-
Nifedipine
-
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
-
Calcium