Calcium Influx Activates Extracellular-regulated Kinase/Mitogen-activated Protein Kinase Pathway through a Calmodulin-sensitive Mechanism in PC12 Cells
Issue date
1999Suggested citation
Egea Navarro, Joaquim;
Espinet Mestre, Carme;
Comella i Carnicé, Joan Xavier;
.
(1999)
.
Calcium Influx Activates Extracellular-regulated Kinase/Mitogen-activated Protein Kinase Pathway through a Calmodulin-sensitive Mechanism in PC12 Cells.
Journal of Biological Chemistry, 1999, vol. 274, núm. 1, p. 75-85.
https://doi.org/10.1074/jbc.274.1.75.
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Show full item recordAbstract
Evidence suggests that membrane depolarization is
able to promote neuronal survival through a sustained,
although moderate, increase in the intracellular calcium.
We have used the PC12 cell line to study the possible
intracellular pathways that can be activated by
calcium influx. Previously, we observed that membrane
depolarization-induced calcium influx was able to activate
the extracellular-regulated kinase (ERK)/mitogenactivated
protein kinase pathway and most of this activation
was calmodulin-dependent. We demonstrated
that a part of the ERK activation is due to the phosphorylation
of the epidermal growth factor receptor. Here,
we show that both the epidermal growth factor receptor
phosphorylation and the Shc-Grb2-Ras activation are
not calmodulin-modulated. Moreover, dominant negative
mutant Ha-ras (Asn-17) prevents the activation on
ERKs by membrane depolarization, suggesting that Ras
and calmodulin are both necessaries to activate ERKs
by membrane depolarization. We failed to observe any
significant induction and/or modulation of the A-Raf,
B-Raf or c-Raf-1 kinase activities, thus suggesting the
existence of a MEK kinase different from the classical
Raf kinases that directly or indirectly can be modulated
by Ca21/calmodulin.