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Calmodulin Modulates Mitogen‐Activated Protein Kinase Activation in Response to Membrane Depolarization in PC12 Cells
Author(s) -
Egea Joaquim,
Espinet Carme,
Comella Joan X.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70062554.x
Subject(s) - mapk/erk pathway , microbiology and biotechnology , calmodulin , trk receptor , depolarization , signal transduction , protein kinase a , phosphorylation , kinase , biology , neurotrophin , mitogen activated protein kinase , chemistry , receptor , biochemistry , biophysics , enzyme
In the absence of neurotrophic factors, chronic depolarization of plasma membrane has been shown to maintain several populations of primary neurons in culture. We report that in the PC12 cell line, depolarization causes Ca 2+ influx through voltage‐gated Ca 2+ channels, which is able to stimulate extracellular‐regulated kinase (ERK) activity. We studied which mediators were responsible for ERK activation resulting from increased levels of Ca 2+ in the cytoplasm and found that calmodulin was involved in this process. The addition of W13, a calmodulin inhibitor, to the culture medium, prevented ERK activation when PC12 cells were depolarized. In addition, we show that high K + treatment did not induce Trk A phosphorylation, thus excluding the possibility of Ca 2+ operating through this receptor to activate the ERK signal transduction pathway. Moreover, although high K + treatment is able to phosphorylate the epidermal growth factor receptor (EGFR) and thus to activate the ERK signal transduction pathway, we demonstrate that W13 did not alter the state of EGFR phosphorylation in conditions that almost completely blocked ERK activation. These data suggest that calmodulin mediates ERK activation induced by increases in intracellular Ca 2+ concentration in PC12 cells by a mechanism that seems to be independent of Trk A and EGFR activation.